Diarrhoea in HIV-infected patients: no evidence of cytokine-mediated inflammation in jejunal mucosa.
OBJECTIVE
To determine whether a mucosal cytokine-mediated inflammatory response is involved in cryptosporidial or microsporidial diarrhoea, as well as in diarrhoea of unknown origin in HIV-infected patients.


METHODS
Prospective study.


METHODS
Jejunal biopsies were obtained from HIV-infected patients with diarrhoea. Controls were HIV-infected and HIV-seronegative patients without diarrhoea. Two biopsies were homogenized immediately and two other biopsies were first cultured for 20 h. Cytokines [tumour necrosis factor (TNF), interleukin (IL)-1 beta, IL-6, IL-8, IL-10], soluble TNF receptors (sTNFR) p55 and p75, and soluble IL-2 receptor (sIL-2R) were assessed in the homogenates and in the supernatants by sandwich enzyme-linked immunosorbent or enzyme-linked binding assays. The cytokine receptors were also measured in serum.


RESULTS
Six HIV-infected patients with cryptosporidiosis, six with microsporidiosis, seven with diarrhoea of unknown origin, seven without diarrhoea, and seven HIV-seronegative patients were eligible. Four patients were excluded because of the presence of other pathogens. No cytokines were detected in immediately homogenized jejunal tissue. Following culture, IL-6 and IL-8 levels were higher in HIV-infected patients with diarrhoea of unknown origin than in HIV-seronegative controls without diarrhoea, although this was not statistically significant. No differences in serum or post-culture supernatant sTNFR p55 and p75 levels existed between the HIV-infected patients with or without diarrhoea. sTNFR, IL-1 beta, IL-10 and the sIL-2R were only detected in low amounts or not at all, and were equally distributed among all patient groups.


CONCLUSIONS
This study indicates that mucosal cytokine-mediated inflammatory responses do not play an important role in the pathogenesis of different types of diarrhoea in HIV-infected patients. These results do not support the use of immunomodulatory therapy in these patients.
Snijders
F
F
Division of Infectious Diseases, Tropical Medicine and AIDS, University of Amsterdam, The Netherlands.
van Deventer
S J
SJ
Bartelsman
J F
JF
den Otter
P
P
Jansen
J
J
Mevissen
M L
ML
van Gool
T
T
Danner
S A
SA
Reiss
P
P
D017088:AIDS-Related Opportunistic Infections / Q000209:etiology / Q000473:pathology; D000328:Adult; D000818:Animals; D003457:Cryptosporidiosis / Q000150:complications / Q000276:immunology; D016207:Cytokines / Q000502:physiology*; D003967:Diarrhea / Q000150:complications* / Q000209:etiology; D005260:Female; D015658:HIV Infections / Q000150:complications*; D015497:HIV-1; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D007583:Jejunum / Q000276:immunology / Q000473:pathology; D008297:Male; D016816:Microsporida; D016881:Microsporidiosis / Q000150:complications / Q000209:etiology; D008875:Middle Aged; D011446:Prospective Studies; D018121:Receptors, Cytokine / Q000378:metabolism
D016207:Cytokines; D018121:Receptors, Cytokine