Trichinosis: Physiologic Factors Possibly Altering the Course of Infection

Abstract

The relative importance, degree of interplay, and mode of action of immunoglobulins and delayed and immediate hypersensitivity in immunity to Trichinella spiralis is not clear. Since several workers have demonstrated the immunogenic nature of antibodies through passive transfer of serum, attempts were made to elucidate a mechanism of action. The direct effect of sera from trichinellainfected rabbits and rats on trichinella larvae were studied with regard to (1) glucose absorption, (2) glucose assimilation, (3) utilization of endogenous carbohydrates, and (4) production of fermentation acids. There was no significant difference in U-14C glucose uptake, tissue labeling patterns, glycogen and trehalose depletion, and acid excretion between control larvae and larvae exposed to immune serum for 48 hr. Specific changes associated with inflamed tissue, such as a reduction in 02 and CO2 tensions, and an increase in hydrogen ion concentration were studied with regard to their importance to worm survival in vitro. The effects of reduced 02 and CO2 tensions on the viability of larvae were inconclusive. In contrast the survival of worms exposed to an acid pH was decreased. Larvae and postlarval worms (recovered from the intestine 24 to 96 hr after infection) maintained for 48 hr at pH 6.0 to 6.5 were less than 50% as viable as controls maintained at a higher pH. Results support the conclusion that antiserum does not directly damage trichinella but may adversely affect the parasite by inducing the development of local acidosis through immunologically mediated inflammation. Such a condition may be involved in worm expulsion during the intestinal phase of trichinosis. Hosts infected with Trichinella spiralis develop a degree of immunity that is dependent in part on reactions leading to the expulsion of the intestinal stages (Denham, 1966; Larsh, 1963, 1968; Despommier and Wostmann, 1968; Denham, 1969). The stage initially contacting defense mechanisms of the host is the infective larva which excysts in the upper gastrointestinal tract and then penetrates the mucosa of the small intestine. Larsh (1963) compared the development of a population of larvae following primary and challenge infections, and observed that with the challenge inoculum some worms developed into stunted adults, fecundity of adult worms was reduced, and intestinal stages were expelled earlier than in control animals. The results suggest that there are nutritional and metabolic disturbances in growing worms that are associated with immune reactions. Received for publication 20 October 1972. * Work was supported by PHS Research Grants AI09348 and AI08491 and Research Fellowship GM44959 from the NIH, and Grant GY2436 from the NSF. t Present address: Program in Physiology, The University of Texas Medical School, Houston, Texas 77025. + Present address: St. Jean's Convent, 196 E. 76 Street, New York, New York 10021. Although acquired resistance to helminths involves more than direct antigen-antibody reactions (Soulsby, 1962; Larsh, 1967, 1968; Tanner, 1968; Gore et al., 1970; Thorson, 1970), immunoglobulins have been implicated in immunity to trichinella (Culbertson and Kaplan, 1938; Oliver-Gonzalez, 1941; Culbertson, 1942; Hendricks, 1953). It is not clear whether antibodies affect the parasite directly. Adverse effects on intestinal stages of trichinella in challenged animals have also been attributed, in part, to an immunologically mediated inflammatory response in the gut mucosa which is unsuitable for worm survival (Larsh, 1967). However, specific conditions associated with inflammation, such as a reduction in oxygen or carbon dioxide, or an increase in hydrogen ion concentration (Menkin, 1956) have not been studied. In the present investigation the following hypotheses were tested: (1) that immune serum, or gamma globulins in such serum, adversely affect the uptake and metabolism of glucose, and (2) that specific alterations in pH and in CO2 and 02 tensions impair the ability of the parasite to survive and thus contribute to acquired resistance.