Hypothesis: An alternative pathway for the regulation of inflammation.

ISTURIZ, MARTÍN; BEIGIER-BOMPADRE, MACARENA; BARRIONUEVO, PAULA; ALVES-ROSA, FERNANDA; PALERMO, MARINA; VULCANO, MARISA

MEDICINA (BUENOS AIRES)

Fundación Revista Medicina

Lugar: Buenos Aires; Año: 2004 vol. 64 p. 235 - 239

0025-7680

Regulation of inflammation is a crucial event since its alteration, such as in sepsis and chronic autoimmune (i.e. rheumatoid arthritis, lupus erythematosus) or infectious diseases (i.e. tuberculosis, leprosy), determines severe tissue damage. Although there is a general consensus that regulation of inflammation results from a balance between proinflammatory and antiinflammatory pathways, we arrived at the conclusion that well known chemoattractants / proinflammatory molecules such as bacterial formyl peptides or immune complexes (IC), could induce, paradoxically, strong antiinflammatory effects. Thus, we demonstrated that N-formyl-methionyl-leucyl-phenylalanine (FMLP) exerted a drastic antiinflammatory effect, inhibiting the secretion of tumor necrosis alpha (TNF-a) induced by lipopolysaccharides, a potent TNF-a inducer. We also determined that in human neutrophils FMLP and IC induced the downregulation of receptors for the Fc portion of IgG (FcgRII and FcgRIIIB). Moreover, FMLP inhibited interferon gamma (IFN-g)-induced FcgRI expression and IC downregulate class II molecules of the major histocompatibility complex on monocytes. Part of these effects were mediated by the release of aspartic-, serin-, or metalloproteases. All these results favor the postulation of a new concept on the regulation of inflammation carried out through an alternative and non conventional pathway, in which a chemoattractant / proinflammatory agent could, under certain circumstances, act as an antiinflammatory molecule.