Inhibition of the cytokine response does not protect against lethal H5N1 influenza infection

Abstract

Because proinflammatory cytokines are markedly elevated during H5N1 influenza virus infection, the "cytokine storm" is hypothesized to be the main cause of mortality. Here, we demonstrate that mice deficient in the hallmark inflammatory cytokines TNF-alpha, IL-6, or CC chemokine ligand 2 succumb to infection with A/Vietnam/1203/04 (H5N1) virus, as do wild-type mice treated with glucocorticoids for suppression of cytokines. Because cytokine inhibition does not protect against death, therapies that target the virus rather than cytokines may be preferable.

Fig. 1.

Mortality and morbidity of mice deficient in TNF-α, IL-6, and CCL2 after inoculation with A/Vietnam/1203/04 influenza virus. Percent survival of mice deficient in TNF-α, TNFR1, or TNFR1 and R2 (A); IL-6 (B); and CCL2 (C).

Fig. 2.

Effect of glucocorticoid treatment on mice inoculated with A/Vietnam/1203/04. (A and B) Percent survival (A) and mean percent weight loss (B) ± SE 5 days after inoculation. n = 5 mice per group.