THE RELATED CYTOKINES INTERLEUKIN-13 AND INTERLEUKIN-4 ARE DISTINGUISHED BY DIFFERENTIAL PRODUCTION AND DIFFERENTIAL-EFFECTS ON T-LYMPHOCYTES

We have compared the production of the related cytokines IL-13 and IL- 4 by T lymphocytes, and the effects of the two cytokines on these cell s, IL-13 and IL-4 production differ in a number of respects, IL-13 is produced at higher levels than IL-4 by activated T lymphocytes, and it s accumulation in the culture medium can be more prolonged, correspond ing partly to differential mRNA accumulation and partly to a preferent ial depletion of IL-4 from the culture medium, Certain inducing combin ations, such as PMA and anti-CD28, stimulate high levels of IL-13 and IL-13 mRNA, but little or no IL-4 or IL-4 mRNA, The ratio of IL-13 to IL-4, both at protein and mRNA levels, is higher in CD8(+) lymphocyte than in CD4(+) lymphocyte populations, Although after in vitro polariz ation of peripheral blood lymphocytes leading to type 1 and type 2 pop ulations, IL-13 is made principally by cells of a type 2 phenotype, as is IL-4; it can also be produced by type 1 CD4(+) and CD8(+) T lympho cyte clones making large amounts of IFN-gamma and very little IL-4. IL -13 and IL-4 exert different effects on T lymphocyte functions, IL-13 does not significantly inhibit the IL-2-induced T lymphocyte productio n of IFN-gamma, RANTES, MIP-1 alpha or MIP-1 beta, nor that of perfori n mRNA, as does IL-4, We have also been unable to demonstrate STAT6 ac tivation by IL-13 on T lymphocytes purified in a number of ways, despi te strong activation of STAT6 by IL-4 in these cells, This is contrary to some previous reports, but is consistent with the notion that the majority of T lymphocytes lack functional IL-13 receptors, A higher an d more prolonged T lymphocyte production of IL-13 than that of IL-4 ma y thus be permissible because IL-13 does not inhibit T-cell functions, Conversely, sustained IL-13 production may be partly due to the absen ce of receptor-mediated depletion of this cytokine.