Inducible nitric oxide synthase (iNOS) plays an important role in mediating
inflammation. In our studies, we found that iNOS-derived NO was significantly increased in the serum samples of 150 patients infected with influenza A virus in comparison with samples of 140 healthy individuals. In human lung epithelial cells,
infection with influenza A virus or stimulation with
poly(I:C) +
interferon-gamma resulted in increased
mRNA and
protein levels of both interleukin-32 and iNOS, with subsequent release of NO. Activated macrophages are also a source of
nitric oxide (NO), which is largely produced by iNOS in response to proinflammatory
cytokines. In this review article, the presented findings have many important implications for understanding the
Influenza A (H1N1) viral pathogenesis, prevention, and treatment. The direct viral cytotoxicity (referred cytopathic effect) is only a fraction of several types of events induced by
virus infection.
Nitric oxide and
oxygen free radicals such as
superoxide anion (O₂⁻˙) are generated markedly in
influenza A (including H1N1) virus-infected host boosts, and these molecular species are identified as the potent pathogenic agents. The mutual interaction of NO with O₂⁻˙ resulting in formation of
peroxynitrite is operative in the pathogenic mechanism of influenza virus
pneumonia. The toxicity and reactivity of
oxygen radicals, generated in excessive amounts mediate the overreaction of the host's immune response against the organs or tissues in which viruses are replicating, and this may explain the mechanism of tissue
injuries observed in influenza virus
infection of various types. The authors revealed the protection that
carnosine and its bioavailable nonhydrolized forms provide against
peroxynitrite damage and other types of viral
injuries in which immunologic interactions are usually involved.
Carnosine (beta-alanyl-
L-histidine) shows the pharmacologic intracellular correction of NO release which might be one of the important factors of natural immunity in controlling the initial stages of influenza A virus
infection (inhibition of virus replication) and virus-induced regulation of
cytokine gene expression. The protective effects of orally applied nonhydrolized formulated species of
carnosine include at least direct interaction with
nitric oxide, inhibition of cytotoxic NO-induced proinflammatory condition, and attenuation of the effects of
cytokines and
chemokines that can exert profound effects on inflammatory cells. These data are consistent with the hypothesis that natural products, such as chicken soup and chicken breast extracts rich in
carnosine and its derivative
anserine (beta-alanyl-1-methyl-L-histidine) could contribute to the pathogenesis and prevention of influenza virus
infections and cold but have a limitation due to susceptibility to enzymatic hydrolysis of
dipeptides with serum
carnosinase and urine excretion after oral ingestion of a commercial chicken extract. The developed and patented by the authors formulations of nonhydrolized in digestive tract and blood natural
carnosine peptide and isopeptide (gamma-glutamyl-
carnosine) products have a promise in the
Influenza A (H1N1) virus
infection disease control and prevention.