Stimulant effect of the immunomodulator MTP-PE on proliferation of monocytic cells in the guinea pig

The effect of a single subcutaneous injection of various doses of the lipophilic muramyl tripeptide MTP-PE on cell proliferation was investigated in autoradiographs of histological sections of various organs of the guinea pig. The animals either received first MTP-PE in saline and then one 3H-thymidine pulse 1 h prior to sacrifice, or they were prelabeled with 3H-thymidine and then received MTP-PE. The number of proliferating cells increased up to between two and fivefold (marginally after 0.3 mg/kg and maximally after 30 mg/kg MTP-PE), but differed in the various organs. In addition, the time of the maximal increase varied between 5 h and 72 h after MTP-PE treatment and also depended on the organ. The majority of proliferating cells were of the monocyte lineage seen in conjunction with the vascular system. They were apparently promonocytes still capable of proliferation. Evidence for this conclusion is derived from (i) the distribution of 1 h-pulse-labeled cells in the various organ compartments in relation to the stimulated proliferation of the bone-marrow cells, and (ii) the distribution of the prelabeled, mainly bone-marrow derived cells, to the various organs. The augmented proliferation of the monocyte lineage is preceded by a dose-dependent, short-lasting increase in the proliferation of some epithelia and also by an increase in body temperature and a transient change in plasma proteins. These effects are part of a limited inflammatory reaction and may contribute to the immunostimulation.