Potentiation of immune responses in mice by a new inosine derivative--methyl inosine monophosphate (MIMP)

• Published in: International journal of immunopharmacology Vol. 14; no. 7; p. 1259
• Main Authors: Sosa, M, Saha, A R, Wang, Y, Coto, J, Giner-Sorolla, A, Hadden, E M, Hadden, J W
• Format: Journal Article
• Language: English
• Published: England 01-10-1992
• Subjects: Adjuvants, Immunologic - pharmacology; Adjuvants, Immunologic - toxicity; Animals; Antibody Formation - drug effects; Antibody-Producing Cells - drug effects; Antibody-Producing Cells - immunology; Female; Hypersensitivity, Delayed; Inosine Monophosphate - analogs & derivatives; Inosine Monophosphate - pharmacology; Inosine Monophosphate - toxicity; Lethal Dose 50; Lymphocyte Activation - drug effects; Mice; Mice, Inbred BALB C; T-Lymphocytes - drug effects; T-Lymphocytes - immunology
• ISSN: 0192-0561
• DOI: 10.1016/0192-0561(92)90062-P

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.