Complement system in nutritional deficiency

Abstract

To break the vicious circle between malnutrition and severe infection which has been linked to the great magnitude of infant deaths worldwide, we have been searching by means of clinical and experimental studies for measures which provide for rapid enhancement of body defenses. Based on clinical observations of malnourished children and the sequence of recovery during nutritional rehabilitation, it is suggested that the complement system is a more important factor during the early stage of nutritional recovery than CMI. In animal experiments using malnourished rats, nutritional deprivation affected various components of the body defense system to various extents, CMI being the most susceptible to influence. The complement system acted to maintain host defense even when CMI was impaired. Also observed was the earlier recovery of serum complement to normal or higher levels as compared with that of CMI. The complement system responded to bacterial infection much earlier than other immunologic responses, even in malnourished rats with depressed CMI. The infected rats showed a much higher rate of de novo synthesis of complement proteins than noninfected rats, and this effect was predominant in the malnourished group. Based on these animal experiments, we attempted to induce rapid heightened resistance to infection in malnourished rats by enhancing the complement system. After administration of proper doses of lentinan or Zn-chlorophyllin, which are known to activate C3 in vitro, to malnourished rats, heightened resistance against bacterial infection was induced together with a heightened complement response. In contrast, after administration of cobra venom factor, which is known to reduce C3 activity both in vitro and in vivo, resistance against bacterial infection was reduced, even in well-nourished rats. In summary, we have analyzed in the malnourished state the mechanism of heightened resistance against bacterial infection after activation of C3 by lentinan or Zn-chlorophyllin. These C3 activators enhanced C3b formation and iC3b formation in vivo, eventually resulting in enhanced interaction of iC3b present on invaders with CR3 on phagocytic cells.