Interleukind release by rat liver macrophages

Tissue mscrophagesof the liver (Kupffer cells) release interleukio-6 (IL-6) in vitro. Since Kupffer cells reside in close proximity to hepatocytes, which ate major target cells of U-6, the regulation of IL-6 release by hepatic macropbager has been investigated in this study. Using the hybrldoma growfbtest to detect IL-5 we foend that Kupffer cells already maximallyrekese 1Me.t endotoxbtconcentrationsaslow as 1.Ong.M.Tl~estimulatedsccretionof 1L_6vesiacreased4-&ld by endotoxin when compared to the mntml macrophagesincubated in serum-containingmedium alone. The preincubation of macrophage; with interferon-y enhanced the capacity of Kupffer cells to respond to endotoxin. The secretion of IL6 could atso be induced by interleukiin (IL)+ and tumor nesroris factor (TNF-a). The most patent inducers, bawever, were the paramyxovirusesNewcastle Disease Vii and Sendai Virus. The release of IL-6 by macrcphages upon sdmulation with en&toxin was almost completely inhibited by 1 pM dexametbasone. Whereas 1M) nM of prostaglandin (PC&) inhibited the release of TNF-a in rat Kupffer cells, it did not affect the secretion of IL-6.

lntedeukin-6 (U-6) ir.a cylokble with multiple biologic-al effects. It promotes bath the diffaemiation and gtoti of a variety of target cell types. As a B-ceu sdm”latory factor, it is responsibk for the terminal differentiation of B lymphocytes (IL&BsF-2) (1,2) and acts as a bybridcatllDlmmocvtoma emwtb factor (3.4). IL.& no. cyte gmw& and diffenakott (1,5,6), but it it&& the gmwtb of primary hepatocyte9 in c&ore (7). The bormoot stimula(cs the gmwIb of bemopoktic stem cells. and itt synergism with interleukCa-3 (IL-3), it supports the


ferred to as its hepatocyte stimtdatoty function (IL. 6/HsF) (IJO). U-6 is produced by many different cell types including fibroblasfs, maaophogcr/monoeytcs, T and B lymphocyter. eodotklial ads. sync&l cells. keratinocytss, and byanumberof hmmr&rivedceUUnes(l,ll-14).

Tbe ~~unioodaeu:e-pha~prote~~ isdepemlettton the availability of IL.6 to hepatcqtes. IL-6 syotiwized by cells outside the liver must tint trarel to the liver to reach its target. I&de the liver, bowever, there is ako a popolation of cells which patticipates in host &fee.% and tissue bomeostasis. Lncated bt the bepatic sbwoid, the Kupffer cells play a pndominant role in the clearaoceof pathogeaic materiel like bacteria, vbwes and circulating tomor cells (15). Earlier studlee have already suggested that livermacrophages might be expeaed toprodw IL.6 (16). With the avaitaMity of a very sensitive bioassay, i.e.,

368 the hybridoma growth test (17). this study attempted to investigate whether, and under which conditions, ret Kupffer cells release IL-6


a”d Methods


Agents used induction Recombinant human IL-6iHPGF (l@ Ulpg) (la), antihuman IL-6 antisenrm end the “wine hybridome cell line B9 were kindly supplied by Dr. L.A. Aerden (Central Laboratory of the Netherlands Red Cross, Amsterdam, The Netherlands). Remmbinsnt murine TNF-a (tntTNFa. 1.2.10’ U/mg, as determined by the L929 cytotoxicity essav (19)) and rabbit serum raised aeainst rmTNF-a



were a generous gift from Dr. G.R. Adolf, Ernst-Boehringer-Institute, Vienna, Austria. Remmbittant human IL-l@ @h&l/?, 5.10’ Ulmg LAF) was provided by Bioge” (Geneva, Switzerland). The. monoclonal antibody aeainst rhlL-16 was the kind aih of Dr. R. Andt’cexn (&etmtent of Internal Medi&, University Hospital, Freiburg, F.R.G.). Recombinant rat interferon-y (rlFN7) WBFkindly supplied by Dr. P.H. van der Meide (Rija wijk, The Netherlands). The endotoxin content of ell eytokines was

Interleukin-6 release by rat liver macrophages.

Tissue macrophages of the liver (Kupffer cells) release interleukin-6 (IL-6) in vitro. Since Kupffer cells reside in close proximity to hepatocytes, w...
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