Uncomplicated
influenza in humans, horses or swine is characterized by massive virus replication in respiratory epithelial cells,
inflammation and an abrupt onset of general and respiratory disease. There is now growing evidence that the so-called early
cytokines produced at the site of
infection mediate many of the clinical and pathological manifestations. Among these
cytokines are
interferon-alpha (IFN-alpha), tumour
necrosis factor-alpha (
TNF-alpha),
interleukin-1 (IL-1) alpha and beta,
interleukin-6 (IL-6),
interleukin-8 (IL-8) and monocyte-attracting
chemokines. This paper reviews: (1) in vivo examinations of the
cytokine profiles during
influenza in mice, humans or swine; (2) in vivo data on the probable role of these
cytokines; and (3) selected in vitro data on
cytokine induction by the influenza virus. Examination of respiratory secretions of experimentally infected humans or animals revealed a brisk and concurrent rise in several of the
cytokines mentioned. Moreover, peak
cytokine levels directly correlated with virus replication and disease. In the mouse model, specific anti-
cytokine strategies have further confirmed the role of
cytokines in
body temperature changes,
anorexia and
lung inflammation. However,
cytokines were clearly not the only factor contributing to disease, and they seemed to be essential for resolution of the
infection. Though influenza virus was shown to induce
cytokines in cell culture, in vitro experiments have also revealed conflicting data. Furthermore, the viral genes or products that are responsible for
cytokine induction are unknown. Exactly this information would make important contributions to our understanding of the genetic basis of viral virulence.