Abstract
The effect of recombinant human interferon-alpha (rHuIFN-α) in vitro and in vivo on mitogen-induced lymphocyte blastogenesis was evaluated in specific-pathogen-free cats. Pre-incubation of isolated feline peripheral blood lymphocytes (PBL) in vitro with either 104 or 103 International Units (U) of rHuIFN-α for 24 h significantly suppressed (P<0.001 and 0.01, respectively) blastogenic responses to the phytomitogens concanavalin A (Con A) and pokeweed mitogen (PWM). Lower doses of IFN (range, 10–10−3 U/ml) neither suppressed nor enhanced mitogenesis. In the absence of phytomitogens, incubation of PBL with 104–102 U (P<0.001) or 10 U (P<0.05) of rHuIFN-α/ml resulted in a significant decrease in incorporation of [methyl-3H] thymidine into newly synthesized cellular DNA. Cultures of PBL exposed continuously for 4 days to rHuIFN-α doses of 104 U/ml or less did not demonstrate specific reductions in cell viability, indicating that the observed antiproliferative actions of IFN apparently were independent of any direct cytotoxic effects.
To investigate the dose-response effects of rHuIFN-α in vivo on lymphocyte blastogenesis, individual groups of cats were evaluated on 3 consecutive days before and then 24 h after each cat was inoculated intramuscularly with either a high dose (106 U/kg), moderate dose (104 U/kg), or a relatively low dose (102 U/kg) of rHuIFN-α. Cats inoculated with 106 U ofrHuIFN-α/kg had significantly reduced (P=0.037) blastogenic responses to Con a at 24 h postinoculation compared to preinoculation values; mean PWM responses were also decreased, but this effect was not statistically significant. In contrast, inoculation of cats with either 104 or 102 U of rHuIFN-α/kg significantly enhanced (P=0.05 or 0.008, respectively) Con A-induced blastogenesis and had no discernible effect on PWM responses. These findings suggest that very high doses of rHuIFN-α given parenterally may be associated with suppression of certain T-cell responses in cats; conversely, much lower doses may be immunoenhancing.
Footnotes
Published as Auburn University Publication No. 2093, College of Veterinary Medicine, Auburn University, AL 36849 (U.S.A.)
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