L'interleukine 12 humaine: propriétés biologiques et potentialités thérapeutiques

Abstract

L'interleukine-12 (ILI2) est une cytokine hétérodimérique au large spectre d'activités biologiques; son rôle principal est de potentialiser l'activité cytotoxique et de participer à la régulation de la prolifération des lymphocytes T et des cellules NK Elle induit la production de l'interféron 1 (INF 1), et favorise la différenciation des cellules auxiliaires de type Th-l . Elle est impliquée dans la surveillance immunologique antitumorale: du fait de sa capacité d'induire une réponse immune efficace contre des tumeurs peu immunogènes, son utilisation potentielle en thérapeutique oncologique suscite à l'heure actuelle un grand intérêt. L'IL12 joue un rôle pivot dans la cascade des cytokines et est une bonne candidate comme adjuvant dans le traitement de certaines manifestations immunopathologiques au cours du développement de maladies infectieuses, notaIilment le déficit immunitaire associé au VIH. Il est clairement établi que cette cytokine intervient dans la phase précoce de la réponse immune contre les infections bactériennes et parasitaires et constitue un messager entre la résistance naturelle et le développement de l'immunité spécifique.

Interleukin-12 (IL12) is a disulfide-linked heterodimeric cytokine originally identified as a product of EBV-transformed B cell lines; monocytes/macrophages are the physiologically most relevant producers of IL12 in response to bacterias or intracellular parasites. Although IL12 has an enhancing effect on the survival and growth of hematopoietic progenitor cells, most of the IL12 biological activity has been described on T and NK cells, on which it induces production of lymphokines, primarily IFNgamma, enhances cytotoxic activity and, in cooperation with other stimuli, increases proliferation. Early during infection, IL12 acts as a proinflammatory cytokine by inducing IFNgamma production from NK and T cells which in rum activates phagocytic cells. IL12 then sets the stage for the ensuing adaptive immune response by stimulating generation of T helper type 1 (Th-1) cells and by activating cell-mediated resistance mechanisms against several pathogens. Several studies have now established that IL-12 plays an early and major role in the resistance to bacterial and parasitic infections by activating macrophages through induction of IFNgamma from NK and T cells. Thus, because of its ability to induce Th-1 responses and efficient cell-mediated immunity, IL12 has several potential therapeutic uses in infectious diseases and in cancer patients. Natural IL12 appears to provide a regulatory link between innate resistance and the development of the antigen-specific adaptive immune response. The recombinant protein also has therapeutic potential because of its activity against tumors and infections, and its effectiveness as an adjuvant enhancing cell-mediated immunity in vaccination.