Gene expression of interleukin-1β during hemodialysis

Abstract

It is still controversial whether the hemodialysis (HD) procedure is an inflammatory process in vivo. Therefore, we studied the gene expression of interleukin-1 beta (IL-1 beta) as a marker of inflammation in peripheral blood mononuclear cells (PBMC) of patients during HD by Northern blotting and polymerase chain reaction. Compared to PBMC separated pre-HD (1.0 densitometric units), the amount of IL-1 beta mRNA was increased in PBMC leaving the dialyzer (12.2 +/- 2 densitometric units, P < 0.01), but was not increased in PBMC re-entering the dialyzer from the systemic circulation (0.6 +/- 0.1 densitometric units) in all 12 patients studied. The maximal amount of IL-1 beta mRNA in PBMC was seen at five minutes after start of HD. There was a significant correlation between the increase in IL-1 beta mRNA and the increase in activated complement C5a (r = 0.71, P < 0.01). HD using less complement-activating membranes (hemophan, polysulfone, polyamide or polyacrylonitrile) resulted in no detectable IL-1 beta mRNA. Furthermore, a monoclonal antibody against human C5a reduced the increase in IL-1 beta mRNA by 83% (P < 0.05), indicating that C5a plays a major role for induction of IL-1 beta mRNA during HD. This study demonstrates that during HD with regenerated cellulose, gene expression for IL-1 beta takes place in PBMC.

Haemodialysis activates phospholipase A2 enzyme

“…However, the invivo observations are more difficult to reconcile with that hypothesis, since only some [38][39][40] but not all [41][42][43] studies reveal increased concentrations of IL-1 P in blood. In line with our observation of a more pronounced PLA 2 activation possibly mediated through IL-1 release with a more complementactivating membrane is the recent report from Schindler et ah [14] demonstrating an increased gene expression of IL-1 (3 in peripheral blood mononuclear cells leaving the dialyser 5 min after start of haemodialysis. These authors found a significant correlation between the increase in IL-ip mRNA and increase in activated complement C5a.…”

“…Previous investigations revealed similar peaks of biological events during the initial 15 min on dialysis. These changes comprise among others, a decline in the leuko-ĉ yte count in peripheral blood, evidence for activation of the complement system, release of TNF and interleukins, including IL-ip and arachidonic acid metabolites, such as PGE 2 , TXB 2 , PAF and HETS [2,[8][9][10][11][12][13][14][15][16][17]. The release of many arachidonic acid derivatives suggests activation of PLA 2 , as shown by the present investigations.…”

“…As a result of blood/membrane interaction several studies reported leukopenia due to complement activation [2,8], increased production of |3 2 -microglobulin [12], interleukin-1 (IL-1), interleukin-6(IL-6), tumour necrosis factor (TNF) [9][10][11]13,14], prostacyclin, thromboxane, platelet activating factor (PAF), hydroxyeicosatetraenoic acids (HETS) [9,[15][16][17] during haemodialysis. Many inflammatory cells release prostaglandins and thromboxanes in situ with cuprophane membranes [9].…”

Prevalence and Characterization of Hepatitis C Virus in Hemodialysis Patients.

“…In addition, the patients with normal liver enzyme levels during HDcan still develop progressive liver disease after renal transplantation (5,15). Expression of interleukin-1 (3 and tumor necrosis factor-oc (TNF-a) as well as expression of their inhibitors such as interleukin-1 0 and soluble receptors of TNF-a have been shown to be elevated in HDpatients (16,17). Such an imbalance between cytokines and their inhibitors mayplay a pivotal role in the multifaceted process of immune dysfunction in HDpatients.…”

“…Since the HCV core region has several epitopes which play a crucial role in the immuneresponse to HCV (25,26), alterations or a deletion in this region in HDpatients can operate on escape from immunepressure, leading to persistence of viral infection. Furthermore, the reduced immunedefense resulting from an imbalance between cytokines and their inhibitors (16,17) might also be involved in viral persistence in HDpatients.…”