Peripheral blood leukocyte alterations in mice induced by a hemoregulatory pentapeptide (HP 5b)

The effects of different doses of a synthetic hemoregulatory pentapeptide, analoguous to an inhibitory factor associated with human granulocytes, on the numbers of peripheral blood leukocytes have been investigated in female C3H mice. Following single injections as well as continuous infusion for 6 days, the numbers of granulocytes in peripheral blood were reduced to about one half of the normal. Maximal effect with single injection was seen with 120 micrograms (10(-5) M), while 1.2 mg (10(-4) M) as one dose only had a slight, temporary effect on the granulocyte numbers in peripheral blood. Upon continuous infusion of 14 micrograms/h (less than 10(-5) M) for 19 days, a stimulation with doubling of the granulocyte numbers was seen instead. The substance also decreased the monocyte numbers in peripheral blood. With prolonged exposure, a relative monocytosis was seen instead. After both single injection and continuous infusion, the pentapeptide increased the lymphocyte numbers in peripheral blood. The thrombocyte numbers were not altered. The decreased granulocyte numbers seemed to be due to a dual mechanism, one reducing proliferation in the maturing compartment which gives a rapid cell reduction, and one mediated through inhibition of the committed stem cells for myelopoiesis, giving a long-lasting reduction in the granulocyte numbers. It is postulated that the pentapeptide has a complex regulatory effect in vivo.