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Interleukin-6 Levels in the Central Nervous System Are Negatively Correlated with Fat Mass in Overweight/Obese Subjects

Research Center for Endocrinology and Metabolism, Department of Internal Medicine (K.S.), Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden

Address all correspondence and requests for reprints to: Dr. John-Olov Jansson, Research Center for Endocrinology and Metabolism, Gröna Stråket 8, Sahlgrenska Sjukhuset, SE-413 45 Gothenburg, Sweden. E-mail: joj{at}medic.gu.se.

Recently, we demonstrated that intracerebroventricular injection of IL-6 increases energy expenditure and decreases body fat in rodents. Therefore, IL-6 may play a role in appetite and body weight control in the central nervous system. In the present study we evaluated cerebrospinal fluid (CSF) and serum IL-6 levels in humans in relation to body fat content and to CSF and serum levels of leptin. Thirty-two healthy overweight/obese male subjects with a body mass index range of 29.3–36.0 kg/m² were studied. Total and sc body fat were measured by dual energy x-ray absorptiometry and computed tomography, respectively. CSF IL-6 levels were in some individuals higher than serum IL-6 levels and correlated negatively with total body weight, sc and total body fat. In contrast, CSF leptin levels were 30–60 times lower than serum leptin levels and correlated positively with serum leptin, body weight, sc and total body fat. Furthermore, there was a negative correlation between CSF IL-6 and leptin. In conclusion, CSF IL-6 differs in many ways from CSF leptin. CSF IL-6 may be locally produced rather than serum derived, and body fat-regulating regions in the central nervous system may be exposed to insufficient IL-6 levels in more severe obesity.

This work was supported by the Swedish Medical Research Council (Grants 9894 and 05239), the Novo Nordisk Foundation, Amgen, Inc., The Assar Gabrielsson Foundation, the Swedish Medical Society, the Gothenburg Medical Society, the Swedish Society for Medical Research, and the European Commission (Framework 5, QLRT-1999-02038).

¹ K.S. and I.W. contributed equally to this study.

Abbreviations: BMI, Body mass index; BW, body weight; CNS, central nervous system; CSF, cerebrospinal fluid; DXA, dual energy x-ray absorptiometry.

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