Induction of serum-borne immunomodulatory factors in B6C3F1 mice by carbon tetrachloride. I. Carbon tetrachloride-induced suppression of helper T-lymphocyte function is mediated by a serum borne factor.

Abstract:

:Following carbon tetrachloride-induced liver injury, hepatotrophic factors are synthesized and released into the serum to facilitate the regeneration of damaged hepatic tissue. We investigated the possibility that immunosuppression could be mediated through induction of a serum factor(s) because in vivo exposure of B6C3F1 mice to carbon tetrachloride selectively inhibits T-cell-dependent immune responses. Addition of mouse serum (5% by volume) obtained from mice treated with carbon tetrachloride (250 or 500 mg/kg/day for 7 days) to naive spleen cell cultures markedly suppressed the sheep red blood cell antibody-forming cell response compared to controls (P < 0.01). Immunosuppression was observed in mice sensitized with sheep red blood cells 48 h, but not 24 or 72 h, following one dose of carbon tetrachloride (1000 mg/kg). Only serum isolated from mice 48 h following exposure to a single dose of carbon tetrachloride (1000 mg/kg) suppressed the antibody-forming cell response when added in vitro to spleen cell cultures. Biodistribution studies using [14C]-labelled carbon tetrachloride demonstrated that accumulation of the [14C]-label was primarily associated with excretory organs (liver, kidneys and lungs) but not with the serum, red blood cells, or spleen. Surprisingly, 24 and 48 h following exposure to [14C]-labelled carbon tetrachloride, an increase in radioactivity was detected in the thymus. The distinct profile of immunosuppressive activity associated with serum isolated from carbon tetrachloride-treated mice and the biodistribution studies clearly demonstrating a negligible amount of carbon tetrachloride or metabolites in the serum strongly implicate the role of a carbon tetrachloride-induced serum borne immunosuppressive factor.

journal_name

Toxicology

journal_title

Toxicology

authors

Delaney B,Kaminski NE

doi

10.1016/0300-483x(93)90083-5

subject

Has Abstract

pub_date

1993-12-15 00:00:00

pages

67-84

issue

1

eissn

0300-483X

issn

1879-3185

pii

0300-483X(93)90083-5

journal_volume

85

pub_type

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