Faecal interleukin-8 and Tumour necrosis factor a concentrations and disease activity in Cystic Fibrosis

Abstract

By speculatively using an ELISA technique optimised for measuring cytokine concentrations in cell culture supernatants, I have demonstrated massively elevated faecal IL-8 and TNFα concentrations in 9 UK patients with cystic fibrosis, and have shown a correlation between lung disease severity and faecal IL-8 concentration. Such an assay had the potential to be a repeatable non invasive gauge of the severity of pulmonary inflammation in these patients. However subsequent assays in 14 Australian CF patients detected no faecal cytokines. The assays used proved to be inaccurate and non linear, and I developed and validated an accurate and linear assay protocol by using newborn calf serum as a sample diluent. With this assay patients with crohn's colitis were shown to have high faecal IL-8 and TNFα concentrations, but 19 patients with CF and patients with pneumonia, asthma, bronchiectasis and healthy control children had no detectable faecal cytokine.

Subsequent experiments showed that pancreatic enzyme supplements efficiently digest both cytokines at both pH8 and pH4.5, that CF patients' faecal flora do not have a major digestive effect on these cytokines, and that when gavaged into rat stomach these cytokines do not pass through the intestine in detectable quantities.

The hypothesis that faecal cytokines are produced in response to high lipase pancreatic enzyme therapy in CF was tested by serially measuring cytokine concentrations in cases and controls as this therapy was commenced. TNFα was detected in no patient or control, but low concentrations of IL-8 were found in one pre exposure sample and in two isolated post exposure samples in three separate patients.

The enzyme dosage in this study was one third of that in the initial UK study and it is possible that a higher enzyme dosage might have replicated those initial results, it is however equally possible that the non linear assay used in the initial study greatly over-estimated the cytokine concentration in that study.

It now seems unlikely that cytokine detected in faeces has it's origins in swallowed pulmonary secretions. It is certain that measurement of faecal IL-8 and TNFα does not give a reliable measure of the severity of pulmonary inflammation in cystic fibrosis.

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