Fiber type specific expression of TNF-alpha, IL-6 and IL-18 in human skeletal muscles Running title: Cytokine Expression is Fiber Type Dependent Peter Plomgaard 1 , Milena Penkowa 2 , Bente K. Pedersen 1 (1) Centre of Inflammation and Metabolism at The Department of Infectious Diseases and The Copenhagen Muscle Research Centre, Rigshospitalet, (2) Centre of Inflammation and Metabolism & Section of Neuroprotection at The Panum Institute All affiliations are within The Faculty of Health Sciences, University of Copenhagen, Denmark Abstract Skeletal muscle is now recognized as an endocrine organ with the capacity to pro- duce signal peptides in response to muscle contractions. Here we demonstrate that resting healthy human muscles express cytokines in a fiber type specific man- ner. Human muscle biopsies from seven healthy young males were obtained from m. triceps, m. quadriceps vastus lateralis and m. soleus. Type I fibers contributed (mean ± SE) 24.0 ± 2.5% in triceps of total fibers, 51.3 ± 2.4% in vastus and 84.9 ± 2.2% in soleus. As expected, differences in the fiber type composition were accompanied by marked differences between the three muscles with regard to MHC I and MHC IIa mRNA expression. Immunohistochemistry demonstrated that tumor necrosis factor (TNF)-α and interleukin (IL)-18 were solely expressed by type II fibers, whereas the expres- sion of IL-6 was more prominent in type I compared to type II fibers. The fiber type specificity was found in triceps, vastus and soleus indicating that the level of daily muscle activity did not influence basal cytokine expression. The specificity of cytokine expression in different muscle fiber types in healthy young males suggests that cytokines may play specific regulatory roles in normal physiology. Key words: soleus; triceps; vastus; muscle biopsy; inflammation Introduction A growing body of literature (33) indicates that cytokines are involved in the reg- ulation of skeletal muscle function. Among cytokines, tumor necrosis factor-α (TNF-α) is the cytokine most prominently linked to muscle pathophysiology. TNF-α has been associated with muscle catabolism and loss of muscle function Cytokine Expression is Fiber Type Dependent • 53 Address correspondence to: Peter Plomgaard, Centre of Inflammation and Metabolism, Rigshospitalet, Section 7641, Blegdamsvej 9, DK-2100, Copenhagen, Denmark Ph: 45 35 45 77 97, Fax: 45 35 45 76 44, Email: plomgaard@dadlnet.dk