A randomized clinical trial evaluating the immunomodulatory effect of convalescent plasma on COVID-19-related cytokine storm.

Evaluating the effect of convalescent plasma (CP) on some cytokine storm indices in severe COVID-19 patients. Totally, 62 patients were randomly assigned into two groups for this clinical trial. Patients in the intervention group received one unit (500 mL) plasma on the admission day plus standard drugs while the controls merely received standard treatments. Eventually, primary and secondary outcomes were evaluated. In the CP group, compared with controls, the mean levels of lymphocytes and IL-10 significantly increased while the levels of IL-6, TNF-α, and IFN-γ decreased (p < 0.05). The length of in-hospital stay, and mortality rate did not significantly reduce in the CP group compared with controls (p > 0.05) while WHO severity scores remarkably improved (p = 0.01), despite the higher frequency of underlying diseases among the CP group (66.7%) vs. controls (33.3%). Although CP has a remarkable immunomodulatory and antiviral potential to improve the cytokine storm and disease severity in COVID-19 patients, it did not considerably affect the mortality rate.

Induction of IL-12 from human monocytes after stimulation with Androctonus crassicauda scorpion venom.

The objective of this study was to evaluate the capacity of venom from Androctonus crassicauda to induce expression/production of interleukin (IL)-12 by isolated human monocytes. For this purpose, isolated human monocytes were exposed to different concentrations of the venom (0.16-20 µg/ml) for varying periods (6, 12, and 24 h). Apart from measures of venom cytotoxicity (i.e., lactase dehydrogenase activity [LDH] release), measures of IL-12 p40 mRNA (by Real-time PCR) of IL-12 release (by ELISA) were performed. The results showed that the venom produced significant concentration- and duration of incubation-dependent cytotoxicity. Expression of IL-12 p40 mRNA was significantly increased at all exposure timepoints relative to that in unexposed cells, but was maximal after 6 h of exposure. At that timepoint, the effect from a dose of 2.5 µg venom/ml provided the maximal increase among all doses tested. At the level of the protein itself, IL-12 production remained almost consistently elevated (vs. unexposed control values) across all exposure timepoints, with the greatest formation again occurring after 6 h of incubation at a dose of 2.5 µg venom/ml. The findings from this study demonstrated that venom from the A. crassicauda scorpion contained active constituents that could induce a sustained activation of human monocytes that was manifested, in part, as promotion of the expression/production of IL-12.

Hemiscorpius lepturus venom induces expression and production of interluckin-12 in human monocytes.

The objective of this study was to evaluate the capacity of the venom from Hemiscorpius lepturus to induce expression and production of interleukin-12 (IL-12) on isolated human monocytes. For this purpose, isolated human monocytes (250,000-300,000 cells/ml) were exposed to different concentrations of the venom (0.625, 1.25, 2.5, 5, 10 and 20 µg/ml) in 96-well plates for varying incubation periods (6, 12, and 24 h). The end point of assessment included LDH cytotoxicity assay, measurement of expression of IL-12,p40 mRNA by real-time PCR, and quantification of IL-12 release using sandwich ELISA technique. The results showed that this venom produced concentration- and time of incubation-dependent cytotoxicity. The level of enhancement of expression and production of IL-12 were found significantly higher with lowest concentration and after 6 h of incubation. The findings demonstrated that the venom from this scorpion contains active constituents which can direct the immune system to produce IL-12.