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1

The effects of endotoxin administration on cytokine production in obstructive jaundice

100%
Dawiskiba J., Zimecki M., Kwiatkowska D., Kuzminski A.
Archivum Immunologiae et Therapiae Experimentalis
|
2001
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vol. 49
|
issue 5
391-398
EN
The aim of this study was to evaluate the effect of lipopolysaccharide (LPS) administration, which mimics a surgical intervention, on the immune status of obstructive jaundiced (OJ) and sham-operated control rats. Rats were given 20 mug LPS intraperitoneally on day 13 following bile duct ligation or sham surgery. We determined serum levels of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) on day 14 after surgery, and spontaneous as well as LPS-induced production of these cytokines in splenocyte and peritoneal exudate cell cultures (PEC). We found that IL-6, but not TNF-alpha, serum concentrations were significantly elevated (4-fold) in OJ rats treated with LPS compared with LPS-untreated OJ rats. In sham-operated rats the differences between the respective groups were not significant. The production of TNF-alpha by splenocyte and PEC cultures was depressed in OJ rats treated with LPS; in particular, a very deep decline was observed in the case of spontaneous TNF-alpha production in PEC cultures. In contrast, TNF-alpha production in LPS-untreated and LPS-treated sham-operated rats did not differ. In the case of IL-6 production by splenocytes and PEC cultures, we observed a significant suppression of this cellular function in both OJ and sham-operated rats treated with LPS when compared with the respective controls. In conclusion, the results indicate that the already depressed cytokine production in OJ rats leads to even deeper hyporeactivity following LPS challenge. Lack of TNF- alpha suppression upon LPS treatment in sham-operated rats suggests that surgery-elicited hyporeactivity is mediated by a different mechanism than that leading to immune hyporesponsiveness in OJ. Our findings may explain the relatively high mortality rates of OJ patients subjected to surgery.
2

Lactoferrin regulates the immune responses in post-surgical patients

76%
Zimecki M., Wlaszczyk A., Wojciechowski R., Dawiskiba J., Kruzel M., Kruzel M. L.
Archivum Immunologiae et Therapiae Experimentalis
|
2001
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vol. 49
|
issue 4
325
EN
The effect of oral administration of lactoferrin (LF) was studied to determine if it could modify post-surgical immune response. The action of lactoferrin was evaluated in 18 LF-treated patients versus 28 placebo counterparts. Patients (women and men, mean age 50 years) were given daily oral doses (20 mg each) of LF for 5 consecutive days prior to thyroid surgery. The following immune response parameters were determined in blood samples taken from the patients one day before, one day after, and 5-7 days following surgery: cell morphology, the proliferative response of peripheral blood mononuclear cells (PBMC) to phytohemagglutinin (PHA), and the spontaneous and lipopolysaccharide (LPS)-induced production of tumor necrosis factor alpha (TNF-) and interleukin 6 (IL-6). As a consequence of the thyroid surgery, the total leukocyte count increased on the postoperative day by about 50% in all patients and the percentage of lymphocytes fell by 26 and 35% in the control vs LF-treated group. The content of neutrophils, on the other hand, elevated on day 1 post-operation by 51 and 68%, respectively. The percent of neutrophil precursors was markedly higher in LF-treated patients, particularly on the day before and the day after surgery (4.1 and 4.8 vs 2.5 and 3.7%, respectively). The post-surgical values were, however, comparable in both groups for neutrophils. The proliferative response of lymphocytes showed a slight decrease in the control group and an increase in the LF-treated patients on day 5 post-operation (20% over control group). LPS-induced TNF- production was higher in LF-treated patients in both one day before and one day following surgery (28 and 24% respectively). LPS-induced IL-6 production was comparable in both placebo and LF-treated patients before surgery, however, on day 1 and 5 following surgery, the production of IL-6 was higher in LF-treated patients by 65 and 27%, respectively. Taken together, the data presented in this study revealed increased immune responsiveness in all patients treated with lactoferrin subjected to the thyroid surgery. This suggests that treatment with lactoferrin could constitute an effective protective measure against post-surgical complications.
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