Methyl inosine monophosphate (MIMP) augments T-lymphocyte mitogen responses and reverses various immunosuppressants.
Methyl inosine monophosphate (MIMP) augments preferentially the in vitro responses of human and murine lymphocytes to a T-cell mitogen such as phytohemagglutinin (PHA) and inconsistently to a B-cell mitogen such as pokeweed or lipopolysaccharide (LPS). In a normal interleukin-2-dependent cell line (CTLL), MIMP showed little or no effect on IL-2 action; however, in a murine CTLL line exhibiting impaired responses to IL-2, MIMP stimulated thymidine incorporation and restored the response to IL-2. MIMP augments the PHA responses of both CD4+ and CD8+ human peripheral blood T-cells. The effect of MIMP to augment the PHA response of human lymphocytes is paralleled by the parent molecule, IMP. MIMP, but not IMP, is resistant to hydrolysis by 5'nucleotidase; thus, MIMP appears to be a protected analogue of IMP which is capable of in vivo action. MIMP (100 micrograms/ml) augments the PHA responses of 15 to 24 elderly humans. MIMP also augments the PHA responses of eight HIV-infected pre-AIDS patients but not of eight AIDS patients. When PHA responses of human lymphocytes are suppressed in vitro by an HIV-derived immunosuppressive peptide, interferon alpha, or prostaglandin PGE2, MIMP (0.1-100 micrograms/ml) progressively restores the depressed response; however, when the suppression is severe (greater than 50%), MIMP cannot restore the response. These data indicate that MIMP potentiates normal T-lymphocyte mitogen responses and restores those impaired by a variety of inflammatory and immunosuppressive influences.
Hadden
E M
EM
Immunopharmacology Division, University of South Florida Medical College, Tampa 33612, USA.
Wang
Y
Y
Sosa
M
M
Coffey
R G
RG
Giner-Sorolla
A
A
Hadden
J W
JW
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors*; D007291:Inosine Monophosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D016898:Interferon-alpha / Q000187:drug effects; D051379:Mice; D008934:Mitogens / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects*
D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D016898:Interferon-alpha; D008934:Mitogens; D007291:Inosine Monophosphate; C076557:methyl inosine monophosphate; D015232:Dinoprostone