Non‐steroidal anti‐inflammatory drugs selectively inhibit cytokine production by NK cells and γδ 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.

Effects of cyclooxygenase inhibitors on parasite burden, anemia and oxidative stress in murineTrypanosoma cruziinfection

“…In fact, recent studies showed that NSAIDs selectively inhibit IFN‐γ and TNF‐ α production in spleen cells Michelin et al . (2005) and natural killer (NK) and γδT cells (Inaoka et al , 2006). However, the high lethality after NSAID treatment could be related to a marked systemic increase in TNF‐α production in a situation analogous to that observed in T. cruzi ‐infected C57BL/6 (Pinge‐Filho et al , 1999) and IL‐10 −/− mice (Hunter et al , 1997).…”

“…It is possible that the inhibition of prostaglandin production observed in our studies did not induce alterations in the production of IL-4 in BALB/c infected with T. cruzi, but might have inhibited the development of protective Th1 response in C57BL/6 mice. In fact, recent studies showed that NSAIDs selectively inhibit IFN-g and TNF-a production in spleen cells Michelin et al (2005) and natural killer (NK) and gdT cells (Inaoka et al, 2006). However, the high lethality after NSAID treatment could be related to a marked systemic increase in TNF-a production in a situation analogous to that observed in T. cruzi-infected C57BL/6 (Pinge-Filho et al, 1999) and IL-10 À/À mice (Hunter et al, 1997).…”

Chagas disease: Present status of pathogenic mechanisms and chemotherapy

“…It is also possible that inhibition of prostaglandin production in C57BL/6 mice inhibited the development of protective Th1 response. In fact, nonsteroidal anti-inflammatory drugs (NSAIDs) selectively inhibit IFN-γ and TNF-α production in spleen cells (Michelin et al, 2005), natural killer (NK) and γδT cells (Inaoka et al, 2006).…”

H1N1 pneumonitis associated with long-term non-steroidal anti-inflammatory drug abuse

“…Inaoka et al 4 went on to examine whether NSAIDs could selectively inhibit cytokine production by innate immune cells; they found that early IFN-γ production by innate immune cells, the most efficient strategy for antiviral defence, was impaired by NSAIDs. They concluded that it was possible that the frequent use of NSAIDs during viral infections may cause an overexuberant acquired immune response to the virus to compensate for the decreased antiviral innate immune responses.…”

“…However, they are also known to have immunosuppressive properties and are a risk factor for development of the systemic inflammatory response syndrome in viral infections 4 5. These cases highlight two examples where NSAID abuse may have been a significant factor in the development of severe pneumonitis secondary to H1N1 influenza.…”