Morphine stimulates mesangial cell TNF-alpha and nitrite production.
BACKGROUND
Intravenous opiate abusers are susceptible to develop heroin and HIV-associated nephropathies; however, the role of opiates in the development of these kidney lesions is not clear. Patients with opiate addiction are prone to recurrent infections.


METHODS
The effect of morphine was studied on the generation of TNF-alpha with or without LPS (lipopolysaccharide) by cultured mouse mesangial cells. In addition, the effect of morphine was evaluated on mesangial cell nitrite production. To evaluate the role of opiate receptors, we studied the effect of naloxone and naltrexone on mesangial cell TNF-alpha and nitrite production. To determine the role of TNF-alpha on mesangial cell nitrite production, we examined the effect of anti-TNF-alpha antibody on morphine-induced nitrite production. Assay of TNF-alpha and nitrite production was carried by ELISA and Griess method respectively.


RESULTS
Morphine alone did not enhance the generation of TNF-alpha by mesangial cells, however, an enhanced (P < 0.001) TNF-alpha production was observed when mesangial cells were first treated with morphine for 18 h and then activated further with LPS. Maximum release of TNF-alpha was seen at a concentration of 10(-12) M of morphine. Opiate receptor antagonists (naloxone and naltrexone) inhibited the effect of morphine. Morphine also amplified (P < 0.0002) the effect of LPS on mesangial cell nitrite production. Anti-TNF-alpha antibody attenuated morphine induced nitrite generation.


CONCLUSIONS
We conclude that morphine stimulates the generation of TNF-infinity by LPS-activated mesangial cells. This effect of morphine seems to be opiate receptor mediated and has a downstream effect in the form of mesangial cell nitrite generation. The present in vitro study provides the basis for a hypothesis that morphine may be playing a role in the development of heroin and HIV-associated nephropathies.
Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, New York 11040, USA.
A A
AA
Kapasi
N
N
Gibbons
J
J
Mattana
P C
PC
Singhal
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002461:Cell Line, Transformed / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced; D015699:HIV Envelope Protein gp120 / Q000502:physiology; D015658:HIV Infections / Q000150:complications; D006556:Heroin Dependence / Q000150:complications; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009573:Nitrites / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D000911:Antibodies, Monoclonal; D004791:Enzyme Inhibitors; D015699:HIV Envelope Protein gp120; D008070:Lipopolysaccharides; D009292:Narcotic Antagonists; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D009270:Naloxone; D009271:Naltrexone; D009020:Morphine; D019331:NG-Nitroarginine Methyl Ester