Nonhuman primates: their role in assessing developmental effects of immunomodulatory agents

There are close physiologic similarities between humans and macaques that m ake them well suited for preclinical testing of biopharmaceutics. These inc lude menstrual cycles of similar length and hormonal control, comparable ce llular and endocrine processes of implantation, and similar timetables of p renatal development. Three teratogenic agents have induced abnormal develop ment of the macaque thymus that is a key organ in the development of the fe tal immune system. Embryonic exposure to triamcinolone acetonide, a potent corticosteroid, during critical periods of thymus development caused marked hypoplasia, depletion of thymic lymphocytes, and reduction of epithelial e lements. Aplasia and hypoplasia of the thymus were a distinct feature of th e "retinoid syndrome" in cynomolgus macaques following exposure to 13-cis-r etinoic acid (Accutane) in early pregnancy, the time of neural crest migrat ion. Experimentally induced zinc deficiency in rhesus macaques from concept ion to 1-year of age caused severe alterations in immunocompetence. More re cent studies have shown that the levels of IgG and IgA in cervicovaginal la vages of the rhesus macaque exhibit specific temporal patterns during the n ormal menstrual cycle. Taken together, theses data suggest that several mac aque species are appropriate animal models for preclinical safety assessmen t of immunomodulatory drugs. Current teratology protocols in these models m ay require slight modifications to adequately assess the safety of these bi ologics.