Stimulatory effects of FK156 in a panel of tests designed to detect changes in immune function.
There is a need to evaluate the utility of experimental models in immune function assessment if these are to be accepted in preclinical safety studies. We have evaluated a panel of tests measuring cellularity and functions of the lymphoid system in the Fischer rat in order to determine whether they would detect immunostimulation, rather than suppression. Injection of the peptide immunostimulant FK156 (D-lactyl-L-alanyl-y-D-glutamyl-(L)-meso-diaminopimelyl- (L)-glycine) increased the numbers of macrophages recovered from the peritoneal cavity, and stimulated their activity, as measured by chemiluminescence, adherence, and secretion of interleukin 1. In vitro, T lymphocytes had an increased background incorporation of tritiated thymidine, increased response to sub-optimal concentrations of concanavalin A, and an increase in secretion of interleukin 2 at optimal concentrations of concanavalin A. There was no change in the proliferative responses of B lymphocytes in vitro. Antibody responses to tetanus toxoid in vivo were increased. These changes were not reflected in consistent, statistically significant alterations in the numbers of lymphocytes bearing either lineage markers or the interleukin 2 receptor as a marker of activation.
Weston
B J
BJ
SmithKline Beecham Pharmaceuticals, Biosciences Research Centre, Epsom, Surrey, U.K.
Henderson
D C
DC
Seal
S
S
Spackman
V
V
Robertson
F
F
Dewdney
J M
JM
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D003960:Diaminopimelic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D007107:Immune System / Q000187:drug effects*; D007159:Immunologic Tests; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D000276:Adjuvants, Immunologic; D003960:Diaminopimelic Acid; C034330:FK 156