Kinins and cytokines in plasma and cerebrospinal fluid of patients with neuropsychiatric lupus.
OBJECTIVE
To evaluate the kinin system components and selected cytokines in plasma and cerebrospinal fluid (CSF) of patients with neuropsychiatric lupus (NPL).


METHODS
We studied 29 women with active NPL and 29 healthy women matched to patients for age. Low (LKg) and high molecular weight kininogen (HKg) and cytokine concentrations [interleukin 1beta (IL-1beta), IL-6, IL-8, IL-10, and tumor necrosis factor-a (TNF-a)] were determined by ELISA. The activities of tissue kallikrein, plasma prekallikrein, and kininase II were assayed by their action on selective substrates.


RESULTS
Compared to controls, patients with NPL presented increased plasma and CSF levels of LKg, HKg, and prekallikrein, increased activity of tissue kallikrein and kininase II, and increased levels of IL-6, IL-10, and TNF-a (p < 0.001 each comparison). IL-1beta levels were increased in patient plasma (p < 0.001), whereas plasma IL-8 levels did not differ from controls. IL-1beta and IL-8 were not detected in CSF of patients or controls.


CONCLUSIONS
The increased levels of kininogen fractions, kallikreins, and kininase II in patient plasma and CSF indicate overactivity of the kinin system, suggesting intense kinin production. Since kinins may induce the production of proinflammatory cytokines including IL-1beta, IL-6, and TNF-a, these findings support the participation of kinins and cytokines in the acute manifestations of NPL. Most of the variables evaluated in patients' CSF increased proportionally in relation to plasma levels. In contrast, the activity of tissue kallikrein in patient CSF increased out of proportion to plasma levels, appearing to be locally synthesized in response to brain involvement.
Dellalibera-Joviliano
Renata
R
Department of Medicine, University of São Paulo, Ribeirão Preto, SP, Brazil.
Dos Reis
Marina Lemos
ML
Cunha
Fernando de Queiroz
Fde Q
Donadi
Eduardo Antonio
EA
D000208:Acute Disease; D000328:Adult; D016207:Cytokines / Q000097:blood* / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000097:blood / Q000134:cerebrospinal fluid; D016753:Interleukin-10 / Q000097:blood / Q000134:cerebrospinal fluid; D015850:Interleukin-6 / Q000097:blood / Q000134:cerebrospinal fluid; D016209:Interleukin-8 / Q000097:blood / Q000134:cerebrospinal fluid; D019679:Kininogen, High-Molecular-Weight / Q000097:blood / Q000134:cerebrospinal fluid; D019728:Kininogen, Low-Molecular-Weight / Q000097:blood* / Q000134:cerebrospinal fluid*; D020945:Lupus Vasculitis, Central Nervous System / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000134:cerebrospinal fluid; D011288:Prekallikrein / Q000134:cerebrospinal fluid; D020840:Tissue Kallikreins / Q000097:blood / Q000134:cerebrospinal fluid; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D019679:Kininogen, High-Molecular-Weight; D019728:Kininogen, Low-Molecular-Weight; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D011288:Prekallikrein; D007703:Peptidyl-Dipeptidase A; D020840:Tissue Kallikreins