scholarly journals Treatment of Experimental Candida Sepsis with a Janus Kinase Inhibitor Controls Inflammation and Prolongs Survival

2015 ◽  
Vol 59 (12) ◽  
pp. 7367-7373 ◽  
Author(s):  
P. Tsirigotis ◽  
N. Papanikolaou ◽  
A. Elefanti ◽  
P. Konstantinou ◽  
K. Gkirkas ◽  
...  
Keyword(s):  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Kinase Inhibitor ◽  
Interleukin 10 ◽  
Janus Kinase ◽  
Jak Inhibitors ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α

ABSTRACTJanus kinases (JAK) are intracellular tyrosine kinases that transduce cytokine-mediated signals to the nucleus, promoting gene expression. Cytokines play a major role in microbial sepsis, which is often associated with uncontrolled inflammation leading to death. JAK inhibitors have been used for the treatment of several autoimmune diseases by modulating immune response, but they have never been tested against microbial sepsis. Ruxolitinib is a small-molecule inhibitor of JAK1/2 proteins, which are involved in the downstream signaling pathway of the vast majority of proinflammatory and anti-inflammatory cytokines. We therefore studied the effect of ruxolitinib in a mouse model of sepsis due toCandida albicans. When ruxolitinib therapy (50 mg/kg [of body weight]/day) was started 1 day before infection, the median survival time was reduced by 3 days, the fungal loads in all organs were higher, the inflammation was significantly less, and serum tumor necrosis factor alpha (TNF-α) and interleukin 10 (IL-10) levels and IL-10/TNF-α ratios were higher than in controls. When ruxolitinib therapy (50 to 1.5 mg/kg/day) was started 1 day after infection, an inverted-U relationship was found, with 6.25 mg/kg/day prolonging median survival time by 6 days, resulting in similar fungal loads, less inflammation, and similar cytokine levels but higher IL-10/TNF-α ratios than the controls. The optimal dose of ruxolitinib controlled infection and prolonged survival with less inflammation than in control animals. Administration of JAK inhibitors may be a promising therapeutic adjunct that needs further investigation.

Resection, biopsy, and survival in malignant glial neoplasms

1993 ◽  
Vol 78 (5) ◽  
pp. 767-775 ◽  
Author(s):  
Bertrand C. Devaux ◽  
Judith R. O'Fallon ◽  
Patrick J. Kelly
Keyword(s):  
Radiation Therapy ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Tumor Resection ◽  
External Beam Radiation ◽  
Newly Diagnosed ◽  
Content Type ◽  
Grade Iii ◽  
Fine Print

✓ Between July, 1984, and October, 1988, 263 patients (163 male, 100 female), aged from 4 to 83 years (mean 52 years), with malignant brain gliomas underwent surgical procedures: stereotactic biopsy in 160 and resection in 103 patients. There were 170 grade IV astrocytomas, 17 grade IV mixed oligoastrocytomas, 44 grade III astrocytomas, 22 grade III mixed oligoastrocytomas, and 10 malignant oligodendrogliomas. Overall median survival time was 30.1 weeks for grade IV gliomas, 87.7 weeks for grade III gliomas, and 171.3 weeks for malignant oligodendrogliomas. Multivariate analysis in 218 newly diagnosed cases revealed that the variables most strongly correlated with survival time were: tumor grade, patient age, seizures as a first symptom, a Karnofsky Performance Scale score of less than 70%, tumor resection, and a radiation therapy dose greater than 50 Gy. The proportions of patients receiving tumor resection versus biopsy in each of these prognosis factor groups were similar. Since most of the 22 patients with midline and brain-stem tumors were treated with biopsy alone, these were excluded. Considering 196 newly diagnosed patients with cortical and subcortical tumors, grade IV glioma patients undergoing resection of the contrast-enhancing mass (as evidenced on computerized tomography and magnetic resonance imaging) and postoperative external beam radiation therapy lived longer than those undergoing biopsy only and radiation therapy (median survival time 50.6 weeks and 33.0 weeks, respectively; Smirnov test, p = 0.0380). However, survival in patients with resected grade III gliomas was no better than in those with biopsied grade III lesions (p = 0.746). The authors conclude that, in selected grade IV gliomas, resection of the contrast-enhancing mass followed by radiation therapy is associated with longer survival times than radiation therapy after biopsy alone.

Vascular endothelial growth factor expression and vascular density as prognostic markers of survival in patients with low-grade astrocytoma

1998 ◽  
Vol 88 (3) ◽  
pp. 513-520 ◽  
Author(s):  
Saleem I. Abdulrauf ◽  
Klaus Edvardsen ◽  
Khang L. Ho ◽  
Xiao Yi Yang ◽  
Jack P. Rock ◽  
...  
Keyword(s):  
Growth Factor ◽  
Survival Time ◽  
Malignant Transformation ◽  
Median Survival ◽  
Median Survival Time ◽  
Tumor Tissue ◽  
Low Grade ◽  
Survival Times ◽  
Content Type ◽  
Fine Print

It has long been recognized that some patients with low-grade astrocytoma may survive for many years, whereas in others the disease follows a more malignant course resulting in a short survival time, usually due to malignant transformation into higher-grade tumors. Object. The aim of this study was to investigate angiogenesis in the initial biopsy specimen of tumor tissue as a biological marker to identify patients with low-grade astrocytoma who are at high risk of malignant tumor transformation or death. Methods. Tumor tissue was studied in 74 consecutively treated adult patients in whom a diagnosis of diffuse supratentorial hemispheric histologically proven fibrillary low-grade astrocytoma was made and who underwent surgery between January 1972 and January 1994. Studies were conducted using monoclonal antibodies to the antigens of the proliferation-associated Ki-67 (MIB-1), factor VIII, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF). The overall 5-year survival rate for the entire patient population was 65%, with a median survival time of 7.5 years. The total mean follow-up period was 6.1 years. All tumors showed a low proliferative potential at the time of the initial operation, as demonstrated by an MIB-1 labeling index of less than 1.5%. Patients with more than seven microvessels in tumor tissue (29 cases) had a shorter survival time (mean 3.8 years) than those with seven or fewer microvessels (mean survival 11.2 years). This difference in survival times was significant by univariate (p = 0.001) and stepwise multivariate analyses (p < 0.001). Tumors with a larger number of microvessels also had a greater chance of undergoing malignant transformation (p = 0.001). Similarly, significant staining for VEGF was correlated with shorter survival times when using univariate (p = 0.003) and multivariate (p = 0.008) analyses and with a greater chance of malignant transformation (p = 0.002). Patients with tumors staining positive for VEGF (39 individuals) had a median survival time of 5.3 years, and those with tumors negative for VEGF (35 patients) had a median survival time of 11.2 years. No association was observed between bFGF, EGF, and survival or malignant transformation. The stepwise multivariate analysis included histological and clinical variables simultaneously. Conclusions. The authors have shown that microvessel density and VEGF levels are independent prognostic markers of survival in fibrillary low-grade astrocytoma. This finding leads them to propose that fibrillary diffuse low-grade astrocytoma is not a single pathological entity but is composed of a spectrum of tumors with differing propensities to undergo malignant transformation that is at least partly based on their inherent angiogenic potential.

scholarly journals In VitroInfection of Bovine Monocytes with Mycoplasma bovis Delays Apoptosis and Suppresses Production of Gamma Interferon and Tumor Necrosis Factor Alpha but Not Interleukin-10

2013 ◽  
Vol 82 (1) ◽  
pp. 62-71 ◽  
Author(s):  
Musa Mulongo ◽  
Tracy Prysliak ◽  
Erin Scruten ◽  
Scott Napper ◽  
Jose Perez-Casal
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Interleukin 10 ◽  
Mycoplasma Bovis ◽  
Blood Monocytes ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACTMycoplasma bovisis one of the major causative pathogens of bovine respiratory complex disease (BRD), which is characterized by enzootic pneumonia, mastitis, pleuritis, and polyarthritis.M. bovisenters and colonizes bovine respiratory epithelial cells through inhalation of aerosol from contaminated air. The nature of the interaction betweenM. bovisand the bovine innate immune system is not well understood. We hypothesized thatM. bovisinvades blood monocytes and regulates cellular function to support its persistence and systemic dissemination. We used bovine-specific peptide kinome arrays to identify cellular signaling pathways that could be relevant toM. bovis-monocyte interactionsin vitro. We validated these pathways using functional, protein, and gene expression assays. Here, we show that infection of bovine blood monocytes withM. bovisdelays spontaneous or tumor necrosis factor alpha (TNF-α)/staurosporine-driven apoptosis, activates the NF-κB p65 subunit, and inhibits caspase-9 activity. We also report thatM. bovis-infected bovine monocytes do not produce gamma interferon (IFN-γ) and TNF-α, although the level of production of interleukin-10 (IL-10) is elevated. Our findings suggest thatM. bovistakes over the cellular machinery of bovine monocytes to prolong bacterial survival and to possibly facilitate subsequent systemic distribution.

Gamma knife surgery for brain metastases in patients harboring four or more lesions: survival and prognostic factors

2005 ◽  
Vol 102 (Special_Supplement) ◽  
pp. 147-150 ◽  
Author(s):  
Taek-Kyun Nam ◽  
Jung-Il Lee ◽  
Young-Jo Jung ◽  
Yong-Seok Im ◽  
Hee-Ye An ◽  
...  
Keyword(s):  
Survival Time ◽  
Gamma Knife ◽  
Median Survival ◽  
Median Survival Time ◽  
Gamma Knife Surgery ◽  
Content Type ◽  
Metastatic Lesions ◽  
Group A ◽  
Group B ◽  
Fine Print

Object. This study was performed to evaluate the role of gamma knife surgery (GKS) in patients with a large number (four or more) of metastatic brain lesions. Methods. The authors retrospectively reviewed the outcome in 130 patients who underwent GKS for metastatic lesions. Eighty-four patients presented with one to three lesions (Group A) and 46 presented with four or more lesions (Group B). The overall median survival time after GKS was 35 weeks. The median survival time in Group A (48 weeks) was significantly longer (p = 0.005) than the survival time in Group B (26 weeks). The recursive partitioning analysis (RPA) class was the only significant prognostic factor identified in multivariate analysis. The median survival for patients in RPA Classes I, II, and III was 72, 48, and 19 weeks, respectively, in Group A and 36 and 13 weeks for Classes II and III in Group B. The number of lesions, tumor volume, whole brain radiotherapy, primary tumor site, age, and sex did not affect survival significantly. Conclusions. It is suggested that GKS provides an increase in survival time even in patients with a large number (four or more) of metastatic lesions. Concerning the selection of patients for GKS, RPA class should be considered as the most important factor and multiplicity of the lesions alone should not be a reason for withholding GKS.

scholarly journals Lipase Precursor-Like Protein Promotes Miltefosine Tolerance in Leishmania donovani by Enhancing Parasite Infectivity and Eliciting Anti-inflammatory Responses in Host Macrophages

2018 ◽  
Vol 62 (12) ◽  
Author(s):  
Deepak Kumar Deep ◽  
Ruchi Singh ◽  
Arpita Kulshrestha ◽  
Saima Wajid ◽  
Poonam Salotra
Keyword(s):  
Leishmania Donovani ◽  
Inflammatory Responses ◽  
Indian Subcontinent ◽  
Interleukin 10 ◽  
Oral Drug ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Antileishmanial Drug

ABSTRACT The oral drug miltefosine (MIL) was introduced in the Indian subcontinent in the year 2002 for the treatment of visceral leishmaniasis (VL). However, recent reports on its declining efficacy and increasing relapse rates pose a serious concern. An understanding of the factors contributing to MIL tolerance in Leishmania parasites is critical. In the present study, we assessed the role of the lipase precursor-like protein (Lip) in conferring tolerance to miltefosine by episomally overexpressing Lip in Leishmania donovani (LdLip++). We observed a significant increase (∼3-fold) in the MIL 50% inhibitory concentration (IC50) at both the promastigote (3.90 ± 0.68 µM; P < 0.05) and intracellular amastigote (9.10 ± 0.60 µM; P < 0.05) stages compared to the wild-type counterpart (LdNeo) (MIL IC50s of 1.49 ± 0.20 µM at the promastigote stage and 3.95 ± 0.45 µM at the amastigote stage). LdLip++ parasites exhibited significantly (P < 0.05) increased infectivity to host macrophages and increased metacyclogenesis and tolerance to MIL-induced oxidative stress. The susceptibility of LdLip++ to other antileishmanial drugs (sodium antimony gluconate and amphotericin B) remained unchanged. In comparison to LdNeo, the LdLip++ parasites elicited high host interleukin-10 (IL-10) cytokine expression levels (1.6-fold; P < 0.05) with reduced expression of the cytokine tumor necrosis factor alpha (TNF-α) (1.5-fold; P < 0.05), leading to a significantly (P < 0.01) increased ratio of IL-10/TNF-α. The above-described findings suggest a role of lipase precursor-like protein in conferring tolerance to the oral antileishmanial drug MIL in L. donovani parasites.

Accelerated fractionated proton/photon irradiation to 90 cobalt gray equivalent for glioblastoma multiforme: results of a phase II prospective trial

1999 ◽  
Vol 91 (2) ◽  
pp. 251-260 ◽  
Author(s):  
Markus M. Fitzek ◽  
Allan F. Thornton ◽  
James D. Rabinov ◽  
Michael H. Lev ◽  
Francisco S. Pardo ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Survival Time ◽  
Median Survival ◽  
Phase Ii ◽  
Median Survival Time ◽  
Radiation Necrosis ◽  
Recurrent Tumor ◽  
Content Type ◽  
Accelerated Fractionation ◽  
Fine Print

Object. After conventional doses of 55 to 65 Gy of fractionated irradiation, glioblastoma multiforme (GBM) usually recurs at its original location. This institutional phase II study was designed to assess whether dose escalation to 90 cobalt gray equivalent (CGE) with conformal protons and photons in accelerated fractionation would improve local tumor control and patient survival.Methods. Twenty-three patients were enrolled in this study. Eligibility criteria included age between 18 and 70 years, Karnofsky Performance Scale score of greater than or equal to 70, residual tumor volume of less than 60 ml, and a supratentorial, unilateral tumor.Actuarial survival rates at 2 and 3 years were 34% and 18%, respectively. The median survival time was 20 months, with four patients alive 22 to 60 months postdiagnosis. Analysis by Radiation Therapy Oncology Group prognostic criteria or Medical Research Council indices showed a 5- to 11-month increase in median survival time over those of comparable conventionally treated patients. All patients developed new areas of gadolinium enhancement during the follow-up period. Histological examination of tissues obtained at biopsy, resection, or autopsy was conducted in 15 of 23 patients. Radiation necrosis only was demonstrated in seven patients, and their survival was significantly longer than that of patients with recurrent tumor (p = 0.01). Tumor regrowth occurred most commonly in areas that received doses of 60 to 70 CGE or less; recurrent tumor was found in only one case in the 90-CGE volume.Conclusions. A dose of 90 CGE in accelerated fractionation prevented central recurrence in almost all cases. The median survival time was extended to 20 months, likely as a result of central control. Tumors will usually recur in areas immediately peripheral to this 90-CGE volume, but attempts to extend local control by enlarging the central volume are likely to be limited by difficulties with radiation necrosis.

The role of minocycline in the treatment of intracranial 9L glioma

1995 ◽  
Vol 82 (4) ◽  
pp. 635-640 ◽  
Author(s):  
Jon D. Weingart ◽  
Eric P. Sipos ◽  
Henry Brem
Keyword(s):  
Controlled Release ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Tumor Resection ◽  
Tumor Implantation ◽  
Content Type ◽  
9L Gliosarcoma ◽  
Controlled Release Polymer ◽  
Fine Print

✓ This study was designed to explore the question of whether minocycline, a semisynthetic tetracycline shown to inhibit tumor-induced angiogenesis, could control the growth of the rat intracranial 9L gliosarcoma. Minocycline was tested alone and in combination with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in vivo. Treatment was started at the time of intracranial implantation of 9L gliosarcoma into male Fischer 344 rats, 5 days later, or after tumor resection. Minocycline was delivered locally with a controlled-release polymer or systemically by intraperitoneal injection. Systemic minocycline did not extend survival time. Local treatment with minocycline by a controlled-release polymer implanted at the time of tumor implantation extended median survival time by 530% (p < 0.001) compared to treatment with empty polymer. When treatment was begun 5 days after tumor implantation, minocycline delivered locally or systemically had no effect on survival. However, after tumor resection, treatment with locally delivered minocycline resulted in a 43% increase in median survival time (p < 0.002) compared to treatment with empty polymer. Treatment with a combination of minocycline delivered locally in a controlled-release polymer and systemic BCNU 5 days after tumor implantation resulted in a 93% extension of median survival time compared to BCNU alone (p < 0.002). In contrast, treatment with a combination of systemic minocycline and BCNU did not increase survival time compared to systemic BCNU alone. These results demonstrate that minocycline affects tumor growth when delivered locally and suggest that minocycline may be a clinically effective modulator of intracranial tumor growth when used in combination with a chemotherapeutic agent and surgical resection.

Cystic glioblastoma multiforme: survival outcomes in 22 cases

2004 ◽  
Vol 100 (1) ◽  
pp. 61-67 ◽  
Author(s):  
Marcos V. C. Maldaun ◽  
Dima Suki ◽  
Frederick F. Lang ◽  
Sujit Prabhu ◽  
Weiming Shi ◽  
...  
Keyword(s):  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Tumor Recurrence ◽  
Tumor Volume ◽  
Matched Cohort ◽  
Content Type ◽  
Imaging Characteristics ◽  
Significant Difference ◽  
Fine Print

Object. The goal of this study was to determine whether the presence of a large tumor cyst was associated with improved outcome in patients undergoing surgery for newly diagnosed glioblastomas multiforme (GBMs) by comparing these patients with a matched cohort of patients with noncystic GBMs in clinical features, tumor imaging characteristics, survival, and time to tumor recurrence after surgery. Methods. A retrospective analysis was conducted in 22 patients by using imaging information and chart reviews of operative reports of GBMs with large cysts (≥ 50% of tumor volume) at The University of Texas M. D. Anderson Cancer Center between 1993 and 2002. Clinical and neurosurgical outcomes and recurrence rates were studied. A statistical comparison was made with a matching cohort of 22 patients with noncystic GBMs. No significant differences in clinical variables were found between the cohort with cystic GBMs and the matched cohort with noncystic GBMs. To avoid bias in preoperative assessment of tumor volume, the tumor burden was compared in patients whose tumors had cysts (excluding the cystic mass) and in patients whose tumors did not contain cysts. There was no statistically significant difference between the two groups (p = 0.8). In patients with cystic GBMs the median survival time after surgery was 18.2 months (95% confidence interval [CI] 11.9–24.5 months) and at 2 years 43% of the patients were still alive. In comparison, in patients with noncystic GBMs, the median survival time was 14.3 months (95% CI 12.1–16.4 months) and only 16% of patients were alive at 2 years. The median time to tumor recurrence was 7.6 months (95% CI 0.01–18 months) in patients harboring cystic GBMs and 4.2 months (95% CI 1.8–6.6 months) in the matched cohort (log-rank test, p = 0.04). In the cystic GBM group, no recurrence was observed in 53% of patients at 6 months, 45% at 1 year, and 38% at 2 years after surgery, whereas the corresponding numbers for the noncystic group were 36, 14, and 9%, respectively. Conclusions. The results indicate that patients harboring a GBM that contains a large cyst survive longer and have a longer time to recurrence than those who lack such a cyst. This is the first such observation in the literature.

scholarly journals Host-Pathogen Interaction and Signaling Molecule Secretion Are Modified in thedpp3Knockout Mutant of Candida lusitaniae

2013 ◽  
Vol 82 (1) ◽  
pp. 413-422 ◽  
Author(s):  
Ayman Sabra ◽  
Jean-Jacques Bessoule ◽  
Vessela Atanasova-Penichon ◽  
Thierry Noël ◽  
Karine Dementhon
Keyword(s):  
Interleukin 10 ◽  
Gene Inactivation ◽  
Physical Contact ◽  
Knockout Mutant ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Candida Lusitaniae

ABSTRACTCandida lusitaniaeis an emerging opportunistic yeast and an attractive model to discover new virulence factors inCandidaspecies by reverse genetics. Our goal was to create adpp3Δ knockout mutant and to characterize the effects of this gene inactivation on yeastin vitroandin vivointeraction with the host. The secretion of two signaling molecules inCandidaspecies, phenethyl alcohol (PEA) and tyrosol, but not of farnesol was surprisingly altered in thedpp3Δ knockout mutant. NO and reactive oxygen species (ROS) production as well as tumor necrosis factor alpha (TNF-α) and interleukin 10 (IL-10) secretion were also modified in macrophages infected with this mutant. Interestingly, we found that the wild-type (WT) strain induced an increase in IL-10 secretion by zymosan-activated macrophages without the need for physical contact, whereas thedpp3Δ knockout mutant lost this ability. We further showed a striking role of PEA and tyrosol in this modulation. Last, theDPP3gene was found to be an essential contributor to virulence in mice models, leading to an increase in TNF-α secretion and brain colonization. Although reinsertion of a WTDPP3copy in thedpp3Δ knockout mutant was not sufficient to restore the WT phenotypesin vitro, it allowed a restoration of those observedin vivo. These data support the hypothesis that some of the phenotypes observed followingDPP3gene inactivation may be directly dependent onDPP3, while others may be the indirect consequence of another genetic modification that systematically arises when theDPP3gene is inactivated.

scholarly journals Efficacy of Lysophosphatidylcholine in Combination with Antimicrobial Agents against Acinetobacter baumannii in Experimental Murine Peritoneal Sepsis and Pneumonia Models

2016 ◽  
Vol 60 (8) ◽  
pp. 4464-4470 ◽  
Author(s):  
R. Parra Millán ◽  
M. E. Jiménez Mejías ◽  
V. Sánchez Encinales ◽  
R. Ayerbe Algaba ◽  
A. Gutiérrez Valencia ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Antimicrobial Agents ◽  
Immune Cell ◽  
Lethal Dose ◽  
Interleukin 10 ◽  
Experimental Models ◽  
Enzyme Linked Immunosorbent Assay ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α

ABSTRACTImmune response stimulation to prevent infection progression may be an adjuvant to antimicrobial treatment. Lysophosphatidylcholine (LPC) is an immunomodulator involved in immune cell recruitment and activation. In this study, we aimed to evaluate the efficacy of LPC in combination with colistin, tigecycline, or imipenem in experimental murine models of peritoneal sepsis and pneumonia. We usedAcinetobacter baumanniistrain Ab9, which is susceptible to colistin, tigecycline, and imipenem, and multidrug-resistant strain Ab186, which is susceptible to colistin and resistant to tigecycline and imipenem. Pharmacokinetic and pharmacodynamic parameters for colistin, tigecycline, and imipenem and the 100% minimal lethal dose (MLD100) were determined for both strains. The therapeutic efficacies of LPC, colistin (60 mg/kg of body weight/day), tigecycline (10 mg/kg/day), and imipenem (180 mg/kg/day), alone or in combination, were assessed against Ab9 and Ab186 at the MLD100in murine peritoneal sepsis and pneumonia models. The levels of pro- and anti-inflammatory cytokines, i.e., tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10), were determined by enzyme-linked immunosorbent assay (ELISA) for the same experimental models after inoculating mice with the MLD of both strains. LPC in combination with colistin, tigecycline, or imipenem markedly enhanced the bacterial clearance of Ab9 and Ab186 from the spleen and lungs and reduced bacteremia and mouse mortality rates (P< 0.05) compared with those for colistin, tigecycline, and imipenem monotherapies. Moreover, at 4 h post-bacterial infection, Ab9 induced higher TNF-α and lower IL-10 levels than those with Ab186 (4 μg/ml versus 3 μg/ml [P< 0.05] and 2 μg/ml versus 3.4 μg/ml [P< 0.05], respectively). LPC treatment combined with colistin, tigecycline, or imipenem modestly reduced the severity of infection byA. baumanniistrains with different resistance phenotypes compared to LPC monotherapy in both experimental models.

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