Effect of prolactin, rIFN-gamma or rTNF-alpha in murine toxoplasmosis.
Mice lethally infected with T. gondii and treated with prolactin (PRL), recombinant interferon gamma (rIFN-gamma) or recombinant tumour necrosis factor (rTNF-alpha) were protected against death, as compared to untreated controls. The protective effect of PRL (0.5-2 mg/kg/twice daily for 12 days) was dose dependent and statistically significant (P < 0.001). The survival was 50% or 40% in mice that received doses of 1 x 10(4) U of rIFN-gamma or 4 x 10(4) U of rTNF-alpha at -2, 0, +2 days before and after infection (P < 0.0001). An increase of time to death, up to 60 days after challenge, and of survival rate (50% up to 70%) were observed in animals treated with PRL in combination with either rTNF-alpha or rIFN-gamma, compared to those that received treatments with the same therapeutic agents alone; however the differences were not statistically significant. In addition, a slight synergistic effect on brain cyst formation, with lower number of Toxoplasma cysts, was observed in mice treated with PRL plus TNF-alpha (P < 0.01), compared with animals that received rTNF-alpha alone (P < 0.05). These data suggest that PRL can regulate in vivo endogenous TNF-alpha production in the cytokine cascade. We conclude that prolactin may play an important role in modulating the host's immune defence against T. gondii opportunistic infection.
Benedetto
N
N
Istituto di Microbiologia, Seconda Università degli Studi di Napoli, Larghetto Sant' Aniello a Caponapoli 2, Naples, Italy.
Folgore
A
A
Galdiero
M
M
Meli
R
R
Di Carlo
R
R
D000328:Adult; D000818:Animals; D004359:Drug Therapy, Combination; D006801:Humans; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D018377:Neurotransmitter Agents / Q000008:administration & dosage; D011388:Prolactin / Q000008:administration & dosage / Q000627:therapeutic use*; D014124:Toxoplasmosis, Animal / Q000401:mortality / Q000628:therapy*; D016781:Toxoplasmosis, Cerebral / Q000401:mortality / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000627:therapeutic use*
D018377:Neurotransmitter Agents; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D011388:Prolactin