Alternative activation of macrophages

The classical pathway of interferon-gamma-dependent activation of macrophages by T helper1 (T,1)-type responses is a well-established feature of cellular immunity to infection with intracellular pathogens, such as Mycobacterium tuberculosis and HIV The concept of an alternative pathway of macrophage activation by the T(H)2-type cytokines; interleukin-4 (IL-4) and IL-13 has gained credence in the past decade, to account for a distinctive macrophage phenotype that is consistent with a different role in humoral immunity and repair In this review, I assess the evidence in favour of alternative macrophage activation in the light of macrophage heterogeneity, and define its limits and relevance to a range of immune and inflammatory conditions.