In vitro antitumor, pro-inflammatory, and pro-coagulant activities of Megalopyge opercularis J.E. Smith hemolymph and spine venom

Contact with stinging spines venom from several Lepidoptera larvae may result in skin lesions. In Mexico, envenomation outbreaks caused by Megalopyge opercularis were reported between 2015 and 2016. The aim of this study was to identify the venomous caterpillars in Nuevo Leon, Mexico and evaluate several biological activities of their hemolymph (HEV) and spine setae (SSV) venoms. M. opercularis was identified by cytochrome oxidase subunit (COI) designed primers. HEV and SSV extracts cytotoxic activity was assessed on the L5178Y-R lymphoma cell line. For apoptotic cells number and apoptosis, cells were stained with acridine orange/ethidium bromide and validated by DNA fragmentation. Human peripheral blood mononuclear cells (hPBMC) cytokine response to the extracts was measured by the cytometric bead array assay. Extracts effect on pro-coagulation activity on human plasma was also evaluated. HEV and SSV extracts significantly inhibited (p < 0.01) up to 63% L5178Y-R tumor cell growth at 125–500 µg/mL, as compared with 43% of Vincristine. About 79% extracts-treated tumor cells death was caused by apoptosis. Extracts stimulated (p < 0.01) up to 60% proliferation of resident murine lymphocytes, upregulated IL-1β, IL-6, IL-8, and TNF-α production by hPBMC, and showed potent pro-coagulant effects. The pharmacological relevance of these venoms is discussed.

Elevated Levels of Cerebrospinal Fluid and Plasma Interleukin-37 in Patients with Guillain-Barré Syndrome

Aims. Interleukin-37 (IL-37) is an anti-inflammatory cytokine. This study aims to investigate the concentrations of plasma and cerebrospinal fluid (CSF) IL-37 in patients with Guillain-Barré Syndrome (GBS).Methods. The levels of plasma and CSF IL-37, IL-17A, IFN-γ, and TNF-αin 25 GBS patients and 20 healthy controls (HC) were determined by enzyme-linked immunoabsorbent assay and flow cytometric bead array assay, respectively. The values of clinical parameters in the patients were also measured.Results. The concentrations of plasma IL-37, IL-17A, IFN-γ, and TNF-αand CSF IL-37 and IL-17A in patients at the acute phase of GBS were significantly higher than those in the HC. The levels of plasma IL-37, IL-17A, IFN-γ, and TNF-αwere positively correlated in those patients, and the levels of CSF IL-37 and IL-17A as well as the levels of plasma TNF-αwere correlated positively with the GBS disability scale scores (GDSs) in those patients. Treatment with intravenous immunoglobulin significantly reduced the levels of plasma IL-37, IL-17A, IFN-γ, and TNF-αin the drug-responding patients.Conclusions. Our findings indicate higher levels of plasma and CSF IL-37 and IL-17A and other proinflammatory cytokines in patients with GBS.

Cytokines of the Th1 and Th2 type in sera of rheumatoid arthritis patients; correlations with anti-Hsp40 immune response and diagnostic markers.

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease which affects approximately 1% of the population worldwide. Recent research on the role of heat shock proteins (Hsps) in RA development indicates that they may have pro- or anti-inflammatory effect, most probably via modulating cytokine secretion. We investigated type Th1 (INFγ, TNFα, IL-2) and type Th2 (IL-10, IL-6, IL-4) cytokine levels in sera of RA patients and healthy controls, using flow cytometric bead array assay, and searched for correlations between the cytokine levels and serum antibodies against bacterial (DnaJ) and human (Hdj1, Hdj2 and Hdj3) Hsp40 proteins, as well as clinical and laboratory parameters. The levels of all cytokines studied were significantly increased in RA patients; the highest increase relative to healthy controls (7-fold) was observed for IL-6 and its levels correlated positively with the antibodies directed to DnaJ and to the C-terminal domain of Hdj2, and with diagnostic parameters (DAS 28, Steinbrocker RTG criteria, ARA/7, ESR, TEN, SW and GH). INFγ levels correlated negatively with DAS 28, ESR, TEN and SW. No correlations were found for TNFα, IL-2 or IL-4. Our results support the hypothesis of Hsp40 involvement in RA as well as indicate that IL-6 serum level is a good marker of the RA activity.