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

Int J Immunopharmacol. 1992 Oct;14(7):1259-66. doi: 10.1016/0192-0561(92)90062-p.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Adjuvants, Immunologic
  • Inosine Monophosphate
  • methyl inosine monophosphate