title: Non-steroidal anti-inflammatory drugs selectively inhibit cytokine production by NK cells and gamma delta T cells.
abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) are known to be risk factors for a systemic inflammatory syndrome in viral infections. Innate immune cells are likely to represent the preferential targets for the deleterious effects of NSAIDs in patients with viral infections. We therefore examined whether various classes of NSAIDs could selectively inhibit cytokine production by innate immune cells. NSAIDs selectively inhibited interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha production by natural killer (NK) and gammadelta T cells with each NSAID displaying its own unique pattern of inhibition, while sparing that by acquired immune cells. These inhibitions were independent on cyclooxygenase inhibition. These NSAIDs directly inhibited the cytokine production by the purified gammadelta T-cell population without involving other cell populations. The selective inhibition of the early generation of IFN-gamma and TNF-alpha from NK and gammadelta T cells by NSAIDs may serve to drive the subsequent acquired immune responses towards a Th2 phenotype, leading to the aggravation of allergic symptoms. Our results provide a mechanism to explain the deleterious effects of NSAIDs on clinical symptoms of viral infections and allergic diseases and suggest more targeted use depending on the type of disease.
authors.affiliation: Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan. minaoka@kyorin-u.ac.jp
authors.forename: Miyuki
authors.initials: M
authors.lastname: Inaoka
authors.forename: Momoko
authors.initials: M
authors.lastname: Kimishima
authors.forename: Ryo
authors.initials: R
authors.lastname: Takahashi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Shiohara
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002019:Bufexamac / Q000494:pharmacology; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007109:Immunity / Q000187:drug effects; D007371:Interferon-gamma / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; D002019:Bufexamac; D007371:Interferon-gamma