Ž . International Immunopharmacology 1 2001 1889–1896 www.elsevier.comrlocaterintimp Preliminary StudyrReport Kinin system in lupus nephritis Renata Dellalibera-Joviliano a , Marina L. Reis b , Eduardo A. Donadi a, ) a DiÕision of Clinical Immunology, Department of Medicine, Faculty of Medicine of Ribeirao Preto, UniÕersity of Sao Paulo, ˜ ˜ ( ) AÕenida Bandeirantes 3900, Monte Alegre, 14049-900 Ribeirao Preto SP , Brazil ˜ b ( ) Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, UniÕersity of Sao Paulo, Ribeirao Preto SP , Brazil ˜ ˜ Received 27 January 2001; accepted 22 May 2001 Abstract Ž . There are few studies regarding the evaluation of the kinin system in patients with systemic lupus erythematosus SLE . Ž . In this study, we evaluated the plasma levels of high-molecular weight kininogen HKg , low-molecular weight kininogen Ž . LKg and plasma kallikrein; the plasma activity of tissue kallikrein and kininase II, and urinary kallikrein and kininase II Ž . activities in patients presenting with active lupus nephritis. A total of 30 patients 29 women aged 21–62 years Ž . median s39 and 30 controls matched to the patients for sex and age were studied. Patients presenting with other underlying diseases or using drugs, which could interfere with the kinin system, were excluded. HKg and LKg levels were indirectly evaluated by ELISA. Plasma kallikrein, tissue kallikrein, and kininase II were evaluated by their enzymatic activity on selective substrates. The Mann–Whitney test was used for statistical analysis. HKg, LKg and plasma kallikrein Ž . levels were significantly increased in patients p -0.001, for each comparison . Similarly, tissue kallikrein and kininase II Ž . activities were significantly increased in plasma and urine of patients p -0.001, for each comparison . In urine, the activities of tissue kallikrein and kininase II were at least seven times higher than those seen in the plasma of patients. These results indicate that the kinin system is involved in the acute manifestations of lupus nephritis. Kinins may facilitate immunecomplex deposition and may induce the release of other pro-inflammatory mediators, including cytokines actively involved in the pathogenesis of lupus nephritis. q 2001 Elsevier Science B.V. All rights reserved. Ž . Keywords: Systemic lupus erythematosus SLE ; Kininogens; Kallikreins; Kininase II; Kinins; Lupus nephritis 1. Introduction The kinin system encompasses a series of proteins and proteases with the ability to produce vasoactive peptides by limited proteolysis. High-molecular Ž . Ž . weight HKg and low-molecular weight LKg kininogens are substrates for plasma and tissue ) Corresponding author. Tel.: q 55-16-602-2566; fax: q 55-16- 633-6695. Ž . E-mail address: eadonadi@fmrp.usp.br E.A. Donadi . Ž . kallikreins, yielding the peptides bradykinin Bk and Ž . Lys-bradykynin Lys-Bk , respectively. Both pep- tides are short-lived bioactive molecules which are rapidly inactivated by kininases. Two major kinin receptors, B and B , are responsible for most kinin 1 2 actions. Plasma prekallikrein is a serine protease mainly synthesized by the liver as zymogen. Most plasma prekallikrein circulates complexed with HKg and is activated to kallikrein by negatively charged surfaces wx 1 . Recently, a cysteine protease present on the membrane of endothelial cells has been reported to 1567-5769r01r$ - see front matter q 2001 Elsevier Science B.V. All rights reserved. Ž . PII: S1567-5769 01 00109-6