Priming the macrophage respiratory burst with IL-4: enhancement with TNF-alpha but inhibition by IFN-gamma.
Pre-exposure to bacterial lipopolysaccharide (LPS) or certain cytokines is known to enhance the ability of murine macrophages to generate a respiratory burst in response to subsequent stimulation, a phenomenon referred to as 'priming'. We report here that the cytokine interleukin-4 (IL-4) can prime murine macrophages. Pretreatment of murine bone marrow-derived macrophages (BMM) with 10 U/ml murine IL-4 for 48 hr was found to enhance the respiratory burst following subsequent stimulation with phorbol myristate acetate (PMA) (10(-6) M) or zymosan (1 mg/ml). Human tumour necrosis factor-alpha (TNF-alpha) (10(-9) M) can also prime BMM for an enhanced respiratory burst and the combination of TNF-alpha and IL-4 resulted in an enhanced (greater than additive) priming effect. In contrast, interferon-gamma (IFN-gamma) (100 U/ml), although by itself capable of priming the BMM respiratory burst, was found to antagonize the priming effects of IL-4. These results demonstrate that IL-4 can be added to the growing list of cytokines capable of modulating the respiratory burst response of macrophages, suggesting a possible role for this cytokine in inflammation and in the host response to infection. The opposing effects of TNF-alpha and IFN-gamma when interacting with IL-4 highlight the difficulties in predicting the effect of a given cytokine in vivo, where potential interactions with other cytokines must be considered.
Phillips
W A
WA
University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Victoria, Australia.
Croatto
M
M
Hamilton
J A
JA
D000818:Animals; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D004357:Drug Synergism; D007371:Interferon-gamma / Q000276:immunology*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000276:immunology*; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma