Potentiation of immune responses in mice by a new inosine derivative--methyl inosine monophosphate (MIMP).
Inosine 5'-methyl monophosphate (MIMP) is a new immunomodulator designed to improve upon the activity of other thymomimetic purines. In Balb/c mice, MIMP was assessed for toxicity and activity on immune responses. The lethal dose for half the mice (LD50) exceeded 500 mg/kg of body weight by both the parenteral and oral routes. At doses of 1-100 mg/kg, the mice showed no visible untoward effects. The antibody response of splenocytes to sheep erythrocytes (SRBC) was measured by IgM plaque-forming cells (PFC) in soft agar under optimal conditions of immunization and challenge. MIMP (1-100 mg/kg) was given by both the intraperitoneal and oral routes (gavage) at the time of SRBC injection and 4 days thereafter. The PFC response was found to be significantly augmented. The maximum effect (approximately 2x) was observed at 50 and 100 mg/kg, via intraperitoneal (i.p.) and oral routes, respectively. Increases (maximally 1.5x) in the responses of splenic lymphocytes to mitogen stimulation with phytohemagglutinin (PHA) and concanavalin A (Con A) were observed under similar conditions of MIMP treatment. SRBC-induced delayed-hypersensitivity (DTH) was also measured under optimal conditions. By both i.p. and oral routes, enhancement of DTH response was produced by the lower doses of MIMP (0.01-1 mg/kg). Again, a second peak of optimum stimulation of DTH response was produced by 50 mg/kg of MIMP when administered by both routes. The effect was observed mainly on the sensitization rather than on the expression phase. MIMP qualifies as an effective immunopotentiator in normal mice.
Sosa
M
M
University of South Florida College of Medicine, Division of Immunopharmacology, Tampa 33612.
Saha
A R
AR
Wang
Y
Y
Coto
J
J
Giner-Sorolla
A
A
Hadden
E M
EM
Hadden
J W
JW
D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D000921:Antibody-Producing Cells / Q000187:drug effects / Q000276:immunology; D005260:Female; D006968:Hypersensitivity, Delayed; D007291:Inosine Monophosphate / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D007928:Lethal Dose 50; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D007291:Inosine Monophosphate; C076557:methyl inosine monophosphate