Cytokine production in muscle tissue of patients with idiopathic inflammatory myopathies.
OBJECTIVE
To study cytokine expression in muscle tissues of patients with inflammatory myopathies and to compare the profiles of patients with polymyositis (PM), inclusion body myositis (IBM), and dermatomyositis (DM).


METHODS
We performed indirect immunohistochemistry studies of muscle tissue sections with a panel of 16 different cytokine-specific monoclonal antibodies, directed against interleukin-1alpha, (IL-1alpha), IL-1beta, IL-1 receptor antagonist (IL-1Ra), IL-2, IL-3, IL-4, IL-6, IL-8, IL-10, IL-13, interferon-gamma (IFN gamma), tumor necrosis factor alpha (TNF alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), transforming growth factor beta1 (TGF beta1), TGF beta2, and TGF beta3 in 5 untreated patients each with PM, DM, and IBM and in 4 normal controls. Fresh frozen muscle tissue sections were fixed in formaldehyde before the procedure. The use of saponin as a detergent to permeabilize the cell membranes enabled identification of intracellular cytokine production.


RESULTS
The most prominent finding was the expression of IL-1alpha observed in all patients but in none of the normal controls. In all patients with PM, DM, and IBM, IL-1alpha was expressed in endothelial cells of capillaries, arterioles, and venules in areas surrounded by inflammatory cells, and also in areas with no or scarce inflammatory cells in both endomysium and perimysium. Furthermore, IL-1alpha was also expressed in mononuclear inflammatory cells in all 15 cases. IL-1beta was observed in inflammatory cells in 10 of the 15 patients but, in contrast to IL-1alpha, it was not expressed in blood vessel walls. TGF beta1, TGF beta2, and TGF beta3 were strongly positive in all 15 patients, but only scattered cells were positive in the normal controls. The remaining cytokines were observed only in relatively few cells and only in occasional patients (although the patients were selected for the presence of large infiltrates), and in none of the controls. The patterns were similar in PM, DM, and IBM.


CONCLUSIONS
Cytokine expression in muscle tissue of patients with inflammatory myopathy is dominated by IL-1alpha, IL-1beta, and TGF beta1-3. The predominant IL-1alpha expression in the blood vessels indicates an importance of the endothelial cells in the inflammatory process in PM, IBM, and DM. A sustained, local release of T cell-derived cytokines may not be a requirement for tissue injury in the inflammatory myopathies. There does not appear to be a qualitative difference in cytokine expression patterns in PM, IBM, and DM.
Lundberg
I
I
Karolinska Hospital, Stockholm, Sweden.
Ulfgren
A K
AK
Nyberg
P
P
Andersson
U
U
Klareskog
L
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002648:Child; D016207:Cytokines / Q000096:biosynthesis*; D003882:Dermatomyositis / Q000209:etiology / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000032:analysis; D008222:Lymphokines / Q000032:analysis; D008297:Male; D008875:Middle Aged; D015846:Monokines / Q000032:analysis; D009132:Muscles / Q000737:chemistry / Q000473:pathology; D009220:Myositis / Q000209:etiology* / Q000378:metabolism*; D018979:Myositis, Inclusion Body / Q000209:etiology / Q000378:metabolism; D017285:Polymyositis / Q000209:etiology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000032:analysis
D016207:Cytokines; D007375:Interleukin-1; D008222:Lymphokines; D015846:Monokines; D016212:Transforming Growth Factor beta