Tumor necrosis factor-alpha and transforming growth factor-beta production by isolated mononuclear cells from the spinal cords of Lewis rats with experimental autoimmune encephalomyelitis.
We demonstrated time course of the number of mononuclear cells (MNCs) isolated from spinal cords (SCs) correlates with the degree of experimental autoimmune encephalomyelitis (EAE) of Lewis rats, and analyzed their tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta production by MNCs, using enzyme-linked immuno sorbent assay and enzyme-linked immuno spot (ELISPOT) assay. The number of MNCs varied from 5 to 620 x 10(4) per SC of normal Lewis rat and Lewis rat with EAE. MNCs increased and reached a peak on day 2 post clinical onset (Day 2), and subsequently declined through the clinical course. The increase of infiltrating MNCs in SCs paralleled the severity of the disease development. TGF-beta 1 in plasma of rats with EAE significantly increased on Day 1 and reached the peak on Day 3. TNF-alpha levels in culture supernatants of MNCs from SCs increased on Day 1, and it decreased from Day 2, and declined on Day 4 when animals began to recover. TGF-beta 1 was not detected in culture supernatant during the whole clinical course. The number of TNF-alpha and TGF-beta 1 producing cells that were detected by ELISPOT assay increased on Day 0, and decreased rapidly after the onset of neurological symptoms. Thus, increase of TNF-alpha appeared in the early phase of the disease and then promptly decreased. In contrast, TGF-beta 1 was activated during the later recovering phase of the disease. We consider that TNF-alpha may play an important role in the pathogenesis of EAE and TGF-beta may inhibit the development of EAE.
Iwahashi
T
T
Department of Medicine (Neurology), Shinshu University School of Medicine, Matsumoto.
Koh
C S
CS
Inoue
A
A
Yanagisawa
N
N
D000818:Animals; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000276:immunology* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha