288. The post-insemination inflammatory response in the ewe

2005 ◽  
Vol 17 (9) ◽  
pp. 121 ◽  
Author(s):  
J. L. Scott ◽  
N. Ketheesan ◽  
P. M. Summers
Keyword(s):  
Inflammatory Response ◽  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tissue Samples ◽  
Gm Csf ◽  
Reproductive Tissues ◽  
Cell Counts ◽  
Macrophage Colony ◽  
Uterine Body

Insemination causes an inflammatory response in the female reproductive tract of many species. The cytokine/leukocyte network initiated during this reaction is believed to enhance reproductive success.1 This study investigated the post-insemination inflammatory response in the ewe. Fifteen nonparous ewes were mated with the same ram for 1 h and their reproductive tracts were collected 3, 6, 18, 24 or 48 h later. Another fifteen ewes were used as controls. Tissue samples and luminal mucus were collected from 10 sites in each reproductive tract and stained with haematoxylin and eosin, Diffquik and immunohistochemically using a monoclonal CD68 antibody to quantify neutrophils, eosinophils and macrophages. Presence of interleukin-8 (IL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF) was investigated using immunohistochemistry and enzyme-linked immunosorbent assay. Neutrophils and macrophages increased in reproductive tissues following insemination. Mean cell counts in 1.5-mm2 tissue of mated (M) and control (C) ewes demonstrated a peak in neutrophils at 6–18 h post-insemination with significant differences (P < 0.05) between mated and controls in the posterior cervix (M = 23.7; C = 4.1) and uterine body (M = 34.5; C = 11.5). Macrophages peaked at 18–24 h with significant differences (P < 0.05) between mated and controls in the vagina (M=13.4; C = 4.6), posterior cervix (M = 10.4; C = 2.7), mid-cervix (M = 8.5; C = 3.0) and ipsilateral mid-uterine horn (M = 14.2; C = 7.9). Neutrophils increased in the lumen of the cervix and uterine body following insemination but macrophage numbers did not change. Insemination did not affect eosinophils. IL-8 and GM-CSF were detected in endometrial epithelial cells in mated and non-mated ewes. Highest concentrations of IL-8 were found in vaginal mucus. Small quantities of GM-CSF were detected in occasional mucus samples. No difference between mated and non-mated ewes was demonstrated for either cytokine. In conclusion, the post-insemination inflammatory reaction in the ewe involves an increase in neutrophils and macrophages in reproductive tissues, with neutrophils crossing the epithelium into the lumen. There was no apparent increase in IL-8 or GM-CSF in response to insemination. (1)Robertson SA et al. (1997) American Journal of Reproductive Immunology 37, 438–442.

Granulocyte - macrophage colony stimulating factor and interleukin-8 in the reproductive tract of ewes following oestrus and mating

2007 ◽  
Vol 19 (4) ◽  
pp. 585 ◽  
Author(s):  
Jennifer L. Scott ◽  
Natkunam Ketheesan ◽  
Phillip M. Summers
Keyword(s):  
Reproductive Tract ◽  
Staining Intensity ◽  
Female Reproductive Tract ◽  
Enzyme Linked Immunosorbent Assay ◽  
Colony Stimulating Factor ◽  
Tissue Samples ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Cytokines produced in the female reproductive tract after mating may enhance reproductive success. The present study investigated the distribution of granulocyte–macrophage colony stimulating factor (GM-CSF) and interleukin (IL)-8 in tissues and luminal secretions from different sites in the reproductive tract of the ewe following oestrus and after natural mating. Fifteen ewes were mated with a ram for 1 h and their reproductive tracts collected 3, 6, 18, 24 or 48 h later. Another 15 ewes were used as oestrous controls. Luminal secretions and tissue samples were collected from seven sites in each reproductive tract. Secretions were analysed by enzyme-linked immunosorbent assay and tissues were stained immunohistochemically using anti-sheep GM-CSF and anti-sheep IL-8 antibodies. Both cytokines were found in luminal and glandular endometrial epithelium and, to a lesser extent, in cervical epithelium; neither was found in the vaginal epithelium. Twice as many (P < 0.05) luminal samples from mated ewes than non-mated ewes were positive for GM-CSF. The vaginal lumen contained significantly higher (P < 0.01) concentrations of IL-8 compared with other sites, irrespective of mating status. Significant differences (P < 0.05) were found in staining intensity of GM-CSF and IL-8 from different sites. Production of GM-CSF and IL-8 by reproductive tissues is likely to contribute to leucocyte infiltration into the ovine reproductive tract.

scholarly journals Bone marrow stromal fibroblasts secrete interleukin-6 and granulocyte- macrophage colony-stimulating factor in the absence of inflammatory stimulation: demonstration by serum-free bioassay, enzyme-linked immunosorbent assay, and reverse transcriptase polymerase chain reaction

Blood ◽  
1992 ◽  
Vol 80 (5) ◽  
pp. 1190-1198 ◽  
Author(s):  
SC Guba ◽  
CI Sartor ◽  
LR Gottschalk ◽  
YH Jing ◽  
T Mulligan ◽  
...  
Keyword(s):  
Human Serum ◽  
Enzyme Linked Immunosorbent Assay ◽  
Stromal Fibroblasts ◽  
Gm Csf ◽  
Normal Human ◽  
Macrophage Colony Stimulating Factor ◽  
Polymerase Chain ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Bone marrow (BM) stromal fibroblasts produce hematopoietic growth factors (HGFs) in response to inflammatory mediators such as tumor necrosis factor-alpha or interleukin-1 alpha (IL-1 alpha). In the absence of such inflammatory stimuli, production of HGFs by BM stromal cells has been problematic and controversial. In vivo, however, basal hematopoiesis maintains blood counts within a normal homeostatic range even in the absence of inflammation, and HGFs are required for progenitor cell differentiation in vitro. To better ascertain the contribution of BM stromal fibroblasts to basal hematopoiesis, we therefore studied HGF production in quiescent BM stromal fibroblasts by three sensitive assays: serum-free bioassay, enzyme-linked immunosorbent assay, and reverse transcriptase polymerase chain reaction. Stromal fibroblasts were cultured in the presence or absence of normal human serum to determine if serum factor(s) present in the noninflammatory (basal) state induce secretion of HGFs. Human serum was found to induce or enhance transcription and secretion of granulocyte- macrophage colony-stimulating factor (GM-CSF) and enhance secretion of constitutively expressed IL-6. In contrast, no secretion of either granulocyte-CSF (G-CSF) or IL-3 was found. These data indicate that factors in normal human serum are active in enhancing GM-CSF and IL-6 production by stromal fibroblasts and suggest that these growth factors contribute to the maintainance of normal, basal hematopoiesis in vivo.

scholarly journals Recombinant human granulocyte-macrophage colony-stimulating factor in combination with standard induction chemotherapy in de novo acute myeloid leukemia

Blood ◽  
1991 ◽  
Vol 77 (4) ◽  
pp. 700-711 ◽  
Author(s):  
P Bettelheim ◽  
P Valent ◽  
M Andreeff ◽  
A Tafuri ◽  
J Haimi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Induction Chemotherapy ◽  
De Novo ◽  
Gm Csf ◽  
Cell Counts ◽  
Macrophage Colony Stimulating Factor ◽  
De Novo Aml ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Based on in vitro data suggesting that recombinant human granulocyte- macrophage colony-stimulating factor (rhGM-CSF) is capable of stimulating acute myeloid leukemia (AML) blast cells to become more sensitive to cell-cycle-specific drugs we conducted a phase I/II study in de novo AML patients (pts). rhGM-CSF (250 micrograms/m2/d, continuous intravenous infusion) was administered in 18 pts suffering from de novo AML in combination with standard induction chemotherapy (3 + 7 = daunorubicin 45 mg/m2 days 1 through 3, cytosine-arabinoside [Ara- C] 200 mg/m2 continuous infusion days 1 through 7). GM-CSF was started 48 or 24 hours before chemotherapy (prephase) in 14 pts. In four pts with high white blood cell counts (WBC) rhGM-CSF was started after chemotherapy-induced cell reduction (WBC less than 30,000/mm3). During prephase GM-CSF induced an increase in neutrophil and blast cell counts in 13 of 14 and 10 of 14 pts, respectively. In vivo recruitment of leukemic cells into drug-sensitive phases of the cell cycle could be demonstrated by multiparameter cell-cycle analyses in peripheral blood (n = 7) and bone marrow (n = 4) specimens. On day 14, complete aplasia was evident in 17 of 18 pts. GM-CSF was administered until recovery from chemotherapy-induced myelosuppression (absolute neutrophil counts, [ANC] greater than 500/mm3). Fifteen pts (83%) achieved complete remission, 12 did so with one cycle. A shorter duration of neutropenia was evident in these pts compared with historical controls (n = 39), (ANC greater than 500/mm3, day 22.5 +/- 3.4 v 25.2 +/- 3.7, P less than .05). Three pts achieved complete remission after a second cycle (same combination of rhGM-CSF and 3 + 7). Two pts died during bone marrow aplasia because of invasive pulmonary aspergillosis. Clinical side effects possibly related to GM-CSF, mainly fever, diarrhea, and weight gain were mild and tolerable (World Health Organization toxicity grade less than or equal to 2). Together, rhGM-CSF recruits kinetically quiescient AML cells in vivo to enter drug-sensitive phases of the cell cycle and promotes early myeloid recovery from aplasia after exposure to standard induction chemotherapy for AML.

scholarly journals Induction of anti-recombinant human granulocyte-macrophage colony- stimulating factor (Escherichia coli-derived) antibodies and clinical effects in nonimmunocompromised patients

Blood ◽  
1994 ◽  
Vol 84 (12) ◽  
pp. 4078-4087 ◽  
Author(s):  
P Ragnhammar ◽  
HJ Friesen ◽  
JE Frodin ◽  
AK Lefvert ◽  
M Hassan ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antibody Response ◽  
Enzyme Linked Immunosorbent Assay ◽  
Clinical Effects ◽  
Immunocompromised Patients ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

The pharmacokinetics of recombinant human granulocyte-macrophage colony- stimulating factor (rhGM-CSF), induction of anti-GM-CSF antibodies, and clinical effects related to the induction of the antibodies were analyzed in patients with metastatic colorectal carcinoma (CRC) who were not on chemotherapy (n = 20, nonimmunocompromised patients). rhGM- CSF (250 micrograms/m2/d; Escherichia coli-derived) was administered subcutaneously for 10 days every month for 4 months. Eight patients with multiple myeloma (MM) on intensive chemotherapy followed by rhGM- CSF treatment were also included (immunocompromised patients). After a single injection of GM-CSF at the first cycle in CRC patients, the maximum calculated concentration (Cmax) was 5.24 +/- 0.56 ng/mL; the half life (T1/2) was 2.91 +/- 0.8 hours; and the area under the concentration curve (AUC) was 30.86 +/- 6.03 hours x ng/mL (mean +/- SE). No anti-GM-CSF antibodies were detected. During the subsequent cycles, 95% of the CRC patients developed anti-GM-CSF IgG antibodies, which significantly altered the pharmacokinetics of rhGM-CSF at the third and fourth cycles with decreased Cmax (2.87 +/- 0.57 ng/mL; P < .05), T1/2 (1.57 +/- 0.2 hours; P < .05), and AUC (14.90 +/- 4.10 hours x ng/mL; P < .005). The presence of anti-GM-CSF antibodies significantly reduced the GM-CSF-induced enhancement of granulocytes, and there was a clear tendency for a decreased increment of monocytes. Antibodies diminished systemic side effects of rhGM-CSF. Only 1 of 8 MM patients showed a very low anti-GM-CSF antibody titer after GM-CSF therapy, as shown by enzyme-linked immunosorbent assay and Western blot. Therefore, in nonimmunocompromised patients, exogenous nonglycosylated GM-CSF induced an anti-GM-CSF IgG antibody response in practically all patients, which seemed to be of clinical significance. In immunocompromised patients, virtually no significant antibody response was shown.

scholarly journals Identification of functionally distinct domains of human granulocyte- macrophage colony-stimulating factor using monoclonal antibodies

Blood ◽  
1991 ◽  
Vol 77 (5) ◽  
pp. 1033-1043 ◽  
Author(s):  
Y Kanakura ◽  
SA Cannistra ◽  
CB Brown ◽  
M Nakamura ◽  
GF Seelig ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Neutralizing Antibodies ◽  
Solid Phase ◽  
Receptor Interaction ◽  
Enzyme Linked Immunosorbent Assay ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a glycoprotein that is required for the survival, growth, and differentiation of hematopoietic progenitor cells. Although the primary structure of GM-CSF is known from cDNA cloning, the relationship between structure and function of GM-CSF is not fully understood. Fifteen different monoclonal antibodies (MoAbs) to human GM-CSF were generated to map immunologically distinct areas of the molecule. Each of the MoAbs was biotinylated and shown by enzyme-linked immunosorbent assay to bind to recombinant GM-CSF that had been affixed to a solid phase. Each of the 15 unconjugated MoAbs was then used to compete with each biotinylated MoAb for binding to GM-CSF. These cross-blocking studies identified eight distinct epitopes of native GM-CSF. Seven of these epitopes were also present in denatured GM-CSF by Western blotting, and four of the epitopes were at least partially conserved on GM-CSF that was reduced in beta-mercaptoethanol. MoAbs to four of eight epitopes neutralized both recombinant (glycosylated and nonglycosylated) and natural human GM-CSF in a GM colony-forming unit (CFU-GM) assay and blocked GM-CSF-induced activation of neutrophils. For most of the antibodies there was a good correlation between neutralizing activity and the capacity to block binding of 125I-GM-CSF to neutrophils or blasts. Non-neutralizing antibodies to one epitope partially blocked binding of 125I-GM-CSF to neutrophils. None of the MoAbs neutralized interleukin-3, G-CSF, or M-CSF. The locations of seven of the epitopes could be partially mapped with regard to the amino acid structure by determining reactivity to GM-CSF synthetic peptides or to human-mouse chimeric GM-CSFs. The neutralizing antibodies were found to map to amino acids 40–77, 78–94, or 110–127. Thus, these MoAbs are useful to identify functional domains of GM-CSF and in identifying regions that are likely to be involved in receptor interaction.

scholarly journals Oestradiol transmission from males to females in the context of the Bruce and Vandenbergh effects in mice (Mus musculus)

Reproduction ◽  
2012 ◽  
Vol 143 (4) ◽  
pp. 539-548 ◽  
Author(s):  
Adam C Guzzo ◽  
Jihwan Jheon ◽  
Faizan Imtiaz ◽  
Denys deCatanzaro
Keyword(s):  
Mus Musculus ◽  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Male Mice ◽  
Reproductive Maturity ◽  
Reproductive Tissues ◽  
Uterine Growth ◽  
Blastocyst Implantation ◽  
Bladder Urine

Male mice actively direct their urine at nearby females, and this urine reliably contains unconjugated oestradiol (E2) and other steroids. Giving inseminated females minute doses of exogenous E2, either systemically or intranasally, can cause failure of blastocyst implantation. Giving juvenile females minute doses of exogenous E2 promotes measures of reproductive maturity such as uterine mass. Here we show that tritium-labelled E2 (3H-E2) can be traced from injection into novel male mice to tissues of cohabiting inseminated and juvenile females. We show the presence of 3H-E2 in male excretions, transmission to the circulation of females and arrival in the female reproductive tract. In males, 3H-E2 given systemically was readily found in reproductive tissues and was especially abundant in bladder urine. In females, 3H-E2 was found to enter the system via both nasal and percutaneous routes, and was measurable in the uterus and other tissues. As supraoptimal E2 levels can both interfere with blastocyst implantation in inseminated females and promote uterine growth in juvenile females, we suggest that absorption of male-excreted E2 can account for major aspects of the Bruce and Vandenbergh effects.

scholarly journals Bone marrow stromal fibroblasts secrete interleukin-6 and granulocyte- macrophage colony-stimulating factor in the absence of inflammatory stimulation: demonstration by serum-free bioassay, enzyme-linked immunosorbent assay, and reverse transcriptase polymerase chain reaction

Blood ◽  
1992 ◽  
Vol 80 (5) ◽  
pp. 1190-1198 ◽  
Author(s):  
SC Guba ◽  
CI Sartor ◽  
LR Gottschalk ◽  
YH Jing ◽  
T Mulligan ◽  
...  
Keyword(s):  
Human Serum ◽  
Enzyme Linked Immunosorbent Assay ◽  
Stromal Fibroblasts ◽  
Gm Csf ◽  
Normal Human ◽  
Macrophage Colony Stimulating Factor ◽  
Polymerase Chain ◽  
Macrophage Colony ◽  
Stimulating Factor

Bone marrow (BM) stromal fibroblasts produce hematopoietic growth factors (HGFs) in response to inflammatory mediators such as tumor necrosis factor-alpha or interleukin-1 alpha (IL-1 alpha). In the absence of such inflammatory stimuli, production of HGFs by BM stromal cells has been problematic and controversial. In vivo, however, basal hematopoiesis maintains blood counts within a normal homeostatic range even in the absence of inflammation, and HGFs are required for progenitor cell differentiation in vitro. To better ascertain the contribution of BM stromal fibroblasts to basal hematopoiesis, we therefore studied HGF production in quiescent BM stromal fibroblasts by three sensitive assays: serum-free bioassay, enzyme-linked immunosorbent assay, and reverse transcriptase polymerase chain reaction. Stromal fibroblasts were cultured in the presence or absence of normal human serum to determine if serum factor(s) present in the noninflammatory (basal) state induce secretion of HGFs. Human serum was found to induce or enhance transcription and secretion of granulocyte- macrophage colony-stimulating factor (GM-CSF) and enhance secretion of constitutively expressed IL-6. In contrast, no secretion of either granulocyte-CSF (G-CSF) or IL-3 was found. These data indicate that factors in normal human serum are active in enhancing GM-CSF and IL-6 production by stromal fibroblasts and suggest that these growth factors contribute to the maintainance of normal, basal hematopoiesis in vivo.

scholarly journals A comparison of treatment of canine cyclic hematopoiesis with recombinant human granulocyte-macrophage colony-stimulating factor (GM- CSF), G-CSF interleukin-3, and canine G-CSF

Blood ◽  
1990 ◽  
Vol 76 (3) ◽  
pp. 523-532 ◽  
Author(s):  
WP Hammond ◽  
TC Boone ◽  
RE Donahue ◽  
LM Souza ◽  
DC Dale
Keyword(s):  
Bone Marrow ◽  
Growth Factors ◽  
Colony Stimulating Factor ◽  
Interleukin 3 ◽  
Gm Csf ◽  
Cell Counts ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Cyclic Hematopoiesis ◽  
Stimulating Factor

Cyclic hematopoiesis in gray collie dogs is a stem cell disease in which abnormal regulation of cell production in the bone marrow causes cyclic fluctuations of blood cell counts. In vitro studies demonstrated that recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and granulocyte colony stimulating factor (G-CSF) all stimulated increases in colony formation by canine bone marrow progenitor cells. Based on these results, gray collie dogs were then treated with recombinant human (rh) GM-CSF, IL-3, or G-CSF subcutaneously to test the hypothesis that pharmacologic doses of one of these hematopoietic growth factors could alter cyclic production of cells. When recombinant canine G-CSF became available, it was tested over a range of doses. In vivo rhIL-3 had no effect on the recurrent neutropenia but was associated with eosinophilia, rhGM-CSF caused neutrophilia and eosinophilia but cycling of hematopoiesis persisted. However, rhG-CSF caused neutrophilia, prevented the recurrent neutropenia and, in the two animals not developing antibodies to rhG- CSF, obliterated periodic fluctuation of monocyte, eosinophil, reticulocyte, and platelet counts. Recombinant canine G-CSF increased the nadir neutrophil counts and amplitude of fluctuations at low doses (1 micrograms/kg/d) and eliminated all cycling of cell counts at high doses (5 and 10 micrograms/kg/d). These data suggest significant differences in the actions of these growth factors and imply a critical role for G-CSF in the homeostatic regulation of hematopoiesis.

scholarly journals Dissecting the inflammatory twitch in allergically inflamed mice

2016 ◽  
Vol 310 (10) ◽  
pp. L1003-L1009 ◽  
Author(s):  
Joshua J. Pothen ◽  
Matthew E. Poynter ◽  
Lennart K. A. Lundblad ◽  
Jason H. T. Bates
Keyword(s):  
Inflammatory Response ◽  
Refractory Period ◽  
Time Course ◽  
Lavage Fluid ◽  
Gm Csf ◽  
Refractory Periods ◽  
Sequence Of Events ◽  
Cell Counts ◽  
Airways Resistance ◽  
Predetermined Time

We have previously advanced the hypothesis that the allergic inflammatory response in the lungs occurs as a self-limited sequence of events that begins with the onset of inflammation and then resolves back to baseline over a predetermined time course (Pothen JJ, Poynter ME, Bates JH. J Immunol 190: 3510–3516, 2013). In the present study we tested a key prediction of this hypothesis, which is that the instigation of the allergic inflammatory response should be accompanied by a later refractory period during which the response cannot be reinitiated. We challenged groups of ovalbumin-sensitized BALB/c mice for 3, 14, 21 and 31 consecutive days with aerosolized ovalbumin. We measured airways responsiveness as well as cell counts and cytokines in bronchoalveolar lavage fluid after the final challenge in subgroups from each group. In other subgroups we performed the same measurements following rest periods and after a final single recall challenge with antigen. We determined that the refractory periods for GM-CSF, KC, and IL-5 are no longer than 10 days, while those for IFNγ and IL-10 are no longer than 28 days. The refractory periods for total leukocytes and neutrophils were no greater than 28 days, while that for eosinophils was more than 28 days. The refractory period for airways resistance was less than 17, while for lung elastance it was longer than 28 days. Our results thus demonstrate that the components of the allergic inflammatory response in the lung have finite refractory periods, with the refractory period of the entire response being in the order of a month.

Immunologic Characteristics of Cytokines in Otitis Media with Effusion

1992 ◽  
Vol 101 (10_suppl) ◽  
pp. 21-25 ◽  
Author(s):  
Tetsuo Himi ◽  
Toshio Suzuki ◽  
Hiroyuki Takezawa ◽  
Hiroyuki Kodama ◽  
Akikatsu Kataura
Keyword(s):  
Otitis Media ◽  
Middle Ear ◽  
Otitis Media With Effusion ◽  
Acute Otitis Media ◽  
Chronic Otitis Media ◽  
Inflammatory Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Gm Csf ◽  
Cytologic Analysis ◽  
Macrophage Colony

Levels of cytokines, interleukin (IL)–1α, IL-1β, tumor necrosis factor (TNF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were investigated in samples of the middle ear effusions (MEEs) from 144 ears with otitis media with effusion (OME) by enzyme-linked immunosorbent assay, followed by cytologic analysis. Middle ear effusions of the acute purulent type contained a significantly higher concentration of cytokines compared with normal control sera (p < .001). Cytokines were observed at lower levels in MEE in adults than in children. Tests of children at the chronic stage of MEE showed higher levels of TNF than IL-1 and GM-CSF. Meanwhile, IL-1β showed significantly higher concentrations in acute purulent types than in serous and mucoid types (p < .01). In cytologic analysis, the mean level of IL-1β was significantly higher in the neutrophil-rich group than in other groups (p < .05). Cytokines possess several biologic properties, some of which are associated not only with acute otitis media but also with chronic otitis media. This study showed that cytokines, especially IL-1β, contribute to infiltration into the middle ear by inflammatory cells. This implies that the persistent presence of cytokines in MEE could be a factor in prolonged OME.

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