Interleukin‐4 and Interferon‐γ: The Quintessence of a Mutual Antagonistic Relationship

Abstract

The two cytokines interleukin (IL)-4 and interferon (IFN)-gamma play major roles in the generation and regulation of immune responses. Central in this respect is their mutually antagonistic functions. First, IL-4 promotes T helper cell type 2 (Th2) differentiation and stability and inhibits Th1-cell differentiation. A direct role of IFN-gamma in Th1-cell differentiation is debatable, whereas inhibition of Th2-cell differentiation and roles in Th1-cell stabilization are well established functions of IFN-gamma. Secondly, IL-4 and IFN-gamma also affect antibody class switch and expression of Fc receptors differentially, which strongly affect the effector mechanisms following antibody production. Thirdly, macrophage activities induced or enhanced by IFN-gamma, such as expression of certain cytokines, surface molecules and enzymes, are antagonized by IL-4. Together, these functions of IL-4 and IFN-gamma place the two cytokines at cardinal positions in the regulation of immune reactions. In this review the known molecular mechanisms underlying the observed functions of IL-4 and IFN-gamma are presented and discussed.

B cells activated in the presence of Th1 cytokines inhibit osteoclastogenesis

“…Induction of many giant cells by co-culture with BIL-2 suggested that IFN-γ had an important role in the inhibitory action, which was confirmed by the use of anti-IFN-γ neutralizing Ab (Figure 4). BIL-2 also expressed cytokines that are known to antagonize IFN-γ mediated activation of macrophage: IL-4, IL-13, 1L-10, and TGF-β (Gazzinelli et al, 1992;Hausmann et al, 1994;Paludan et al, 1997;Paludan et al, 1998). However, none of these could reverse IFN-γ mediated inhibition of osteoclastogenesis.…”

“…BIL-2 express cytokines that are known to antagonize IFN-γ mediated activation of macrophage: IL-4, IL-13, IL-10, and TGF-β (Gazzinelli et al, 1992;Hausmann et al, 1994;Paludan et al, 1997;Paludan et al, 1998). We tested if these cytokines can antagonize the effect of IFN-γ on osteoclasts, too.…”

Analysis of Tumor-Host Interactions by Gene Expression Profiling of Lung Adenocarcinoma Xenografts Identifies Genes Involved in Tumor Formation

“…5). IFN-g and IL-4 exert opposite effects on the regulation of immune responses, with IFN-g repressing IL-4 expression (16) and IL-4 antagonizing macrophage activities induced or enhanced by IFN-g (17). Activation of the Ras-mitogen-activated protein kinase pathway in T-helper type 2 cells has been shown to alter IL-4R function directly (18), although our data show a correspondence between the mutant k-ras expression signature and IL-4-induced genes (Fig.…”

Immune and other factors modulating host resistance against gastrointestinal nematode parasites in sheep

“…DUOX2 gene expression in the lungs has been responsive for the production of cytokine IFN-γ (Th1 pathway), while DUOX1 has been linked to the production of cytokine IL4 (Th2 pathway) (Harper et al, 2005). One interesting point is that a positive association between IFN-γ and IL4 expression was noted, despite the fact that these cytokines have been shown to have antagonistic functions (Paludan, 1998;Lees et al, 2011). Lees et al (2011) have linked the expression of host oxidants and antioxidants in response to the parasite infection, showing that IL4 appears to be strongly linked to a proliferation of immune cells, as well as to the induction or suppression of the two arms of the host oxidant and antioxidant response, respectively.…”