Cytokine Profile in Patients with Progressive Multiple Sclerosis and Its Association with Disease Progression and Disability.Kallaur AP, Oliveira SR, Simão AN, Alfieri DF, Flauzino T, Lopes J, de Carvalho Jennings Pereira WL, de Meleck Proença C, Borelli SD, Kaimen-Maciel DR, Maes M, Reiche EM.
AbstractInflammation is the driving force for brain injury in patients with multiple sclerosis (MS). The objective of the present study is to delineate the serum cytokine profile in patients with progressive MS in a Southern Brazilian population compared with healthy controls and patients with relapsing-remitting MS (RRMS) and its associations with disease progression and disability.
We included 32 patients with progressive MS, 126 with RRMS, and 40 healthy controls. The patients were evaluated using the Expanded Disability Status Scale (EDSS) and magnetic resonance imaging (MRI) with gadolinium. Serum interleukin (IL)-1β, IL-6, IL-12, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-10, IL-4, and IL-17 levels were assessed using an enzyme-linked immunosorbent assay.
IL-1β, IL-6, TNF-α, IFN-γ, IL-17, IL-4, and IL-10 levels were higher in progressive MS than in controls. Increased IL-1β and IFN-γ and decreased IL-12 and IL-4 levels were found in progressive MS compared with RRMS. Patients with progressive MS with disease progression presented higher TNF-α, IFN-γ, and IL-10 levels than those without disease progression. Patients with progressive MS with disease progression showed a higher frequency of positive gadolinium-enhanced lesions in MRI; higher TNF-α, IFN-γ, and IL-17 levels; and decreased IL-12 levels compared with RRMS patients with progression. There was a significant inverse correlation between IL-10 levels and EDSS score in patients with progressive MS. The results underscore the complex cytokine network imbalance exhibited by progressive MS patients and show the important involvement of TNF-α, IFN-γ, and IL-17 in the pathophysiology and progression of the disease. Moreover, serum IL-10 levels were inversely associated with disability in patients with progressive MS.
Figure: T cell immunity
So the T cells never left? And if you have been following our blog for some time, you'd agree that the T cell/B cell box set is prime time watching without the cliffhanger ending.
But, what do we have extra from this group?
- There is an imbalance in the cytokine pathway in progressive disease, this includes Th1 (IFN-γ), Th2 (IL-4, IL-10), Th17 (IL-17) and Treg (IL-10) cytokines.
- Over the short-term (five years) progressive patients had increased TNF-α, IFN-γ, and IL-10 levels compared with those without disease progression.
- Serum IL-10 levels were inversely correlated with the disability of progressive MS patients and therefore an endogenous anti-inflammatory response is essential.
I'll be adding this to the other tidbits of knowledge gleaned over the years: 1) MS is an autoimmune disorder; 2) T cell activity, whether it be good (IL-10, TGF-β) or bad (IL-1, IL-2, TNF-α, IFN-γ) plays an important role in MS; 3) There is no predefined end point, ergo immunosupression/immune modulation should work at all stages of disease (and should be heeded even in progressive trials).