Depletion of endogenous interleukin-10 augments interleukin-1 beta secretion by Mycobacterium bovis BCG-reactive human cells.
In this study, we found evidence that the interleukin-10 (IL-10) protein is functionally relevant in Mycobacterium bovis BCG-induced cytokine synthesis, as neutralization of endogenously synthesized IL-10 in human cells activated with BCG resulted in a two- to threefold increase in the level of IL-1 beta. When exogenous recombinant human IL-10 was added to human mononuclear cells, a significant reduction of BCG-induced IL-1 beta secretion was observed. This inhibitory effect was not attributed to a cytotoxic effect, since trypan blue exclusion studies indicated no loss of cell viability in the presence of IL-10, and it was specific, as it was completely abolished in the presence of anti-IL-10 neutralizing monoclonal antibody while an irrelevant antibody used as a control had no effect. Taken together, these are the first studies that demonstrate that the depletion of endogenous IL-10 via anti-IL-10 antibody results in a very significantly enhanced BCG-induced IL-1 beta secretion and that the addition of exogenous IL-10 to human mononuclear cells stimulated with BCG inhibits IL-1 beta production. Further experimental work is needed to determine if the neutralization of IL-10 activity via anti-IL-10 antibody indeed enhances cytokine synthesis in vivo. However, the present results may be of importance, since the use of anti-IL-10 antibody could presumably contribute to the protective immunity induced by BCG against tuberculosis via an increase in cytokine synthesis that would amplify antimicrobial systems.
Méndez-Samperio
P
P
Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, I.P.N., México, D.F., México.
Garcia-Martinez
E
E
Hernandez-Garay
M
M
Solis-Cardona
M
M
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015536:Down-Regulation; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D009163:Mycobacterium bovis / Q000276:immunology*; D009500:Neutralization Tests; D011994:Recombinant Proteins / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D011994:Recombinant Proteins; D016753:Interleukin-10