Cytokine expression in allergic inflammation:: systematic review of in vivo challenge studies

BACKGROUND: Allergic inflammatory responses are driven by cells of the immune system that rely on cytokines to regulate the activity of other immune and structural cells. Objective: To review published studies to ( 1) identify cytokines consistently increased after allergen challenge in atopic patients and ( 2) investigate temporal variation in cytokine expression. Methods: A PUBMED systematic search was used to extract data from studies involving analysis of cytokine expression in fluids or biopsies following in vivo allergen challenge in atopic patients. Results: Data were extracted from 82 studies. There were no consistent reports of cytokine protein increase in fluids of patients at 0-1 h after challenge. At 4 - 12 h, the chemokines eotaxin, macrophage inflammatory protein-1alpha, RANTES (regulated on activation normal T cell expressed and secreted) and interleukin (IL)-8 have all been consistently reported to be up-regulated. At 18 - 24 h after challenge, the lymphokines IL-4, IL-5 and IL-13, as well as the proinflammatory cytokines granulocyte - macrophage colony-stimulating factor, tumour necrosis factor-alpha and IL-6 are consistently increased when compared with the respective control value. There were no reports of up-regulation in interferon-gamma protein and mRNA and in IL-2 mRNA. Conclusion: The expression of granulocyte - macrophage colony-stimulating factor is consistently increased in tissues at 4 - 12 h after challenge. The influence of this cytokine on antigen capture and presentation by dendritic cells should be further investigated. Additionally, allergen challenge studies are needed that investigate the expression of macrophage-derived chemokine and thymus-regulated and activation-regulated chemokine in tissues of atopic patients. Blocking the effects of these lymphocyte-specific chemokines might provide new therapeutic approaches for the control of allergic inflammation.