Effect of the antiviral compound MDL 20,610 on some aspects of murine immune function.
At physiologically relevant concentrations an antiviral compound should not perturb the host's ability to mount an immune response against the infecting virus or some other opportunistic pathogen. The purpose of this study was to evaluate the immunomodulatory activity of the antiviral compound MDL 20,610 using murine models. When tested in vitro at the limit of aqueous solubility (6 microM), MDL 20,610 has no significant effect on neutrophil function as assessed by cell migration against FMLP and LTB4 gradients, myeloperoxidase secretion or 0.-2 production. In addition, 6 microM MDL 20,610 has no significant effect on macrophage function as determined by 0.-2 production, Ia and Mac-1 antigen expression and expression of Fc gamma receptors. Finally, MDL 20,610 does not significantly affect in vivo (1-100 mg/kg/day) NK cell activity or DTH to oxazolone; but treatment of mice with 50 or 100 mg MDL 20,610/kg/day significantly (P less than 0.01) enhances SRBC IgM antibody synthesis. These data indicate that MDL 20,610 is relatively devoid of immunomodulatory activity.
Kenny
M T
MT
Merrell Dow Research Institute, Indianapolis, IN 46268-0470.
Dulworth
J K
JK
Torney
H L
HL
Cheng
W D
WD
Roberds
S L
SL
Graham
M C
MC
D000276:Adjuvants, Immunologic; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D005260:Female; D006968:Hypersensitivity, Delayed; D007107:Immune System / Q000187:drug effects*; D007075:Immunoglobulin M / Q000096:biosynthesis; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D011725:Pyridines / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D000998:Antiviral Agents; D007075:Immunoglobulin M; D011725:Pyridines; C050725:MDL 20610