Adolescent intermittent ethanol (AIE) sensitized fever in male Sprague Dawley rats exposed to poly I:C in adulthood.
Brain Behav Immun
; 120: 82-97, 2024 Aug.
Article
in En
| MEDLINE
| ID: mdl-38777284
ABSTRACT
Fever plays an indispensable role in host defense processes and is used as a rapid index of infection severity. Unfortunately, there are also substantial individual differences in fever reactions with biological sex, immunological history, and other demographic variables contributing to adverse outcomes of infection. The present series of studies were designed to test the hypothesis that a history of adolescent alcohol misuse may be a latent experiential variable that determines fever severity using polyinosinicpolycytidylic acid (poly IC), a synthetic form of double-stranded RNA that mimics a viral challenge. Adult male and female Sprague Dawley rats were injected with 0 (saline) or 4 mg/kg poly IC to first establish sex differences in fever sensitivity in Experiment 1 using implanted radiotelemetry devices for remote tracking. In Experiments 2 and 3, adolescent males and females were exposed to either water or ethanol (0 or 4 g/kg intragastrically, 3 days on, 2 days off, â¼P30-P50, 4 cycles/12 exposures total). After a period of abstinence, adult rats (â¼P80-96) were then challenged with saline or poly IC, and fever induction and maintenance were examined across a prolonged time course of 8 h using implanted probes. In Experiments 4 and 5, adult male and female subjects with a prior history of adolescent water or adolescent intermittent ethanol (AIE) were given saline or poly IC, with tissue collected for protein and gene expression analysis at 5 h post-injection. Initial sex differences in fever sensitivity were minimal in response to the 4 mg/kg dose of poly IC in ethanol-naïve rats. AIE exposed males injected with poly IC showed a sensitized fever response as well as enhanced TLR3, IκBα, and IL-1ß expression in the nucleus of the solitary tract. Other brain regions related to thermoregulation and peripheral organs such as spleen, liver, and blood showed generalized immune responses to poly IC, with no differences evident between AIE and water-exposed males. In contrast, AIE did not affect responsiveness to poly IC in females. Thus, the present findings suggest that adolescent binge drinking may produce sex-specific and long-lasting effects on fever reactivity to viral infection, with preliminary evidence suggesting that these effects may be due to centrally-mediated changes in fever regulation rather than peripheral immunological mechanisms.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Poly I-C
/
Rats, Sprague-Dawley
/
Ethanol
/
Fever
Limits:
Animals
Language:
En
Journal:
Brain Behav Immun
Journal subject:
ALERGIA E IMUNOLOGIA
/
CEREBRO
/
PSICOFISIOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
United States
Country of publication:
Netherlands