Methyl inosine monophosphate: a potential immunotherapeutic for early human immunodeficiency virus (HIV) infection.
MIMP is a new thymomimetic purine under development for immunorestorative therapy. Lymphocytes were obtained from eight patients with acquired immunodeficiency disease (AIDS), eight with symptomatic pre-AIDS (ARC), and 22 normal controls and were stimulated in vitro with phytohemagglutinin (PHA). AIDS patients (mean CD4 counts of 40) showed PHA responses less than 10% of control while ARC patients (mean CD4 counts of 544) showed responses approximately 50% of the control responses. MIMP (0.1, 1, 10 and 100 micrograms/ml) progressively augmented the PHA responses in all these groups. The augmentation of the responses of the leukocytes of AIDS patients while statistically significant was minimal. The augmentation of the responses of ARC patients was significant and their maximal responses approached control levels. The effect of 1 micrograms/ml MIMP was comparable with that observed with indomethacin (10(-6) M) and interleukin-2 (IL2 - 4 units/ml) and was additive with each of these stimulants. In a parallel manner, MIMP restored the suppression of control lymphocytes induced by the immunosuppressive 17 amino acid fragment of the P41 peptide of HIV. In vivo experiments showed that MIMP significantly delayed death in a murine FLV AIDS model at a dose of 1 mg/kg by the oral or parenteral route. MIMP is under preclinical development for early HIV disease to forestall progression to AIDS by attenuating virus-induced immunosuppression.
Hadden
J W
JW
Department of Medicine, University of South Florida Medical College, Tampa 33612.
Ongradi
J
J
Specter
S
S
Nelson
R
R
Sosa
M
M
Monell
C
C
Strand
M
M
Giner-Sorolla
A
A
Hadden
E M
EM
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D000818:Animals; D005260:Female; D005622:Friend murine leukemia virus; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007291:Inosine Monophosphate / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D007376:Interleukin-2 / Q000494:pharmacology; D007942:Leukemia, Experimental / Q000188:drug therapy; D008214:Lymphocytes / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D010835:Phytohemagglutinins
D000276:Adjuvants, Immunologic; D007376:Interleukin-2; D010835:Phytohemagglutinins; D007291:Inosine Monophosphate; C076557:methyl inosine monophosphate; D007213:Indomethacin