Somatostatin inhibits pro-inflammatory cytokine secretion from rat hepatic stellate cells.
OBJECTIVE
Activated hepatic stellate cells (HSCs) have been implicated in hepatic fibrosis. Somatostatin (SOM) has an immunomodulatory role. The aim of this study was to assess the secretion of pro-inflammatory cytokines by HSCs and to determine the effect of SOM on the secretion of these mediators.


METHODS
Activated rat HSCs were evaluated for their secretion of IL-1beta, IL-8, and TNF-alpha using ELISA. RNA protection assay was used to determine cytokine mRNA levels. The expression of chemokine and cytokine mRNA and the secretion of these mediators were assessed following incubation with SOM or octreotide.


RESULTS
HSCs spontaneously secreted IL-1beta, IL-8, and TNF-alpha. This secretion was augmented following stimulation by IL-1beta and TNF-alpha. SOM inhibited the spontaneous and TNF-alpha-induced secretion of IL-1beta, IL-8, and TNF-alpha and suppressed the expression of IL-1beta and TNF-alpha mRNA. Octreotide suppressed the secretion of IL-1beta and IL-8.


CONCLUSIONS
These observations indicate that SOM exerts an inhibitory immunomodulatory effect on HSCs.
Lang
Alon
A
Department of Gastroenterology and Liver Diseases, Chaim Sheba Medical Center, Tel-Hashomer, Israel. langda@barak-online.net
Sakhnini
Emad
E
Fidder
Herma H
HH
Maor
Yaakov
Y
Bar-Meir
Simon
S
Chowers
Yehuda
Y
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects; D006728:Hormones / Q000494:pharmacology*; D007155:Immunologic Factors / Q000494:pharmacology*; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D007728:Kupffer Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
D016207:Cytokines; D006728:Hormones; D007155:Immunologic Factors; D007375:Interleukin-1; D016209:Interleukin-8; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013004:Somatostatin