Effects of the Immune System

The majority of in vitro models commonly used are devoid of immune system factors; that is, antimicrobial effects are studied in an environment that does not contain the host defense factors. The antimicrobial effect may thus be underestimated, because organisms are free from the inhibitory action of such immune system factors as leukocytosis, phagocytosis, and immunoglobulins.

Shah [22] employed a model that incorporated fresh human blood from healthy volunteers in an effort to replicate in vivo immune system effects. The model consisted of a glass chamber (similar to the one-compartment model previously described) with an inner cell suspended within. The inner cell, composed of plexiglass, was enclosed at each end with membrane filters designed to allow diffusion of antibiotics. Heparinized human blood was incorporated into the inner chamber, and the outer chamber contained a nutrient medium. The bacterial inoculum was injected into the inner chamber, and antibiotics were administered into the outer vessel.

Use of this model in a study of imipenem against Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa revealed that in the presence of blood alone, the bacterial count was reduced by 90-99%, but in all cases bacterial regrowth was noted. As expected, addition of antibiotic decreased the time to achieve 99% reduction of the bacterial inoculum, and the final bacterial count was decreased in comparison to that obtained in antibiotic-free models. Although the use of blood as a medium allowed incorporation of some aspects of the human immune system, the full range of host defense factors was not included in the model.

Incorporation of blood as a medium into in vitro models has not been widely employed, most likely due to the logistical concerns of working with human blood. However, it should be noted that the lack of an immune system in typical in vitro models is advantageous in some respects, in that the effect of antibiotic exposure alone on the development of bacterial resistance may be measured. Also, results from in vitro models lacking immune system effects may be satisfactorily applied to infection occurring in neutropenic hosts, although, again, not without some concerns over the clinical applicability of these results.

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