Interferon-?, induced nitric oxide-mediated

NITRERGIC STIMULANTS mimic, or cause the production and release of nitric oxide (NO), which is an important mediator that is synthesized on demand. The actions of nitric oxide are very widespread, and imbalance is likely to be involved in a number of disease states. Nitric oxide synthase (NOS) has a widespread distribution in the body, and isoforms are recognized specifically constitutive and inducible (iNOS) forms. Both forms are cytosolic, Ca /calmodulin and NADPH-dependent, and inhibited by L-arginine derivatives. Induction of iNOS is by various inflammatory cytokines, particularly those stimulated by bacterial lipopolysaccarides, including tumour necrosis factor a. interferon 7 and interleukin 1 p. Induction of iNOS only is inhibited by GLUCOCORTICOIDS. 

Other possible modes of action may centre on stimulation of T cells (this occurred with the live aroA mutant of A. salmonicida Marsden et al., 1996), which introduces the role of cellular and innate rather than humoral immunity as the mode of action. For this, examples include A. hydrophila LPS (Baba et al., 1988) and E. tarda ECPs (Lee et al., 2010). Of course, there could be involvement of humoral, cell-mediated and innate immune parameters as stated for the i.p. administration of a live auxotrophic aroA mutant of A. hydrophila with effectiveness against furunculosis in rainbow trout (Vivas et al, 2004). Other possibilities include the evidence that one commercial formalized whole cell V. anguillarum vaccine induces Mx gene (these are inducible by Type I interferons and have a role in antiviral activity) expression in Atlantic salmon after administration intraperitoneally (Acosta et al., 2004). In another example, vaccination with P. damselae subsp. piscicida cells were found to enhance the nitric oxide response, i.e. the production of reactive nitrogen intermediates with their antimicrobial activities, to infection with the pathogen, and is correlated with the level of protection (Acosta et al., 2005). There was inhibition of F columnare adhesion to the skin of immersion vaccinated eel (Mano et al., 1996). Finally, mention will be made of a possible mechanism of protection of V. anguillarum vaccines that may well involve the inhibition of bacterial attachment by unknown factors in the skin mucus (Kawai and Kusuda, 1995). 

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