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.
Istituto di Microbiologia, Seconda Università degli Studi di Napoli, Larghetto Sant' Aniello a Caponapoli 2, Naples, Italy.
N
N
Benedetto
A
A
Folgore
M
M
Galdiero
R
R
Meli
R
R
Di Carlo
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