I think TNF is just not being properly regulated in MS. TNF is a normal, necessary part of the immune system, but it is part of the inflammatory immune system, so it needs to be tightly regulated.
Here is a quote from the prior study you posted.
"In the normal physiological state,expression of TNF is low..."
In the title to the study you just posted it states that TNF is elevated in MS.
"Tumor necrosis factor is elevated in progressive multiple sclerosis and causes excitotoxic neurodegeneration."
I think there are a few reasons for the elevated TNF. One reason would be that MS patients have high levels of TNF secreting dendritic cells, as the following study confirms.
J Neuroimmunol. 1999 Sep 1;99(1):82-90.
Multiple sclerosis is associated with high levels of circulating dendritic cells secreting pro-inflammatory cytokines.
Huang YM, Xiao BG, Ozenci V, Kouwenhoven M, Teleshova N, Fredrikson S, Link H.
“Recent evidence emphasises a pivotal role for dendritic cells (DC) in the control of immunity by priming and tolerising T cells. DC capture and process antigens, express co-stimulatory molecules, migrate to lymphoid organs and secrete cytokines to initiate immune responses…Patients with MS had higher levels of IFN-gamma, TNF-alpha and IL-6 secreting DC than healthy subjects…”
Another reason may be the inability to properly metabolize vitamin B12. In the following study the researchers found that vitamin B12 (cobalamin) deficiency is accompanied by overproduction of TNF.
Eur J Haematol. 2001 Aug;67(2):123-7.
Human cobalamin deficiency: alterations in serum tumour necrosis factor-alpha and epidermal growth factor.
Peracchi M, Bamonti Catena F, Pomati M, De Franceschi M, Scalabrino G.
"In humans, as in rats, cobalamin concentration appears to be correlated with the synthesis and release of TNF-alpha and EGF in a reciprocal manner, because cobalamin deficiency is accompanied by overproduction of TNF-alpha and underproduction of EGF..."
There may however be another reason why low levels of vitamin B12 are associated with elevated TNF. The same enzymes that are responsible for the binding and transport of vitamin B12 (protease), are also involved in the regulation of TNF, as the following studies confirm.
Degradation and inactivation of plasma tumor necrosis factor-alpha by pancreatic proteases in experimental acute pancreatitis.
Alsfasser G., B. Antoniu, S.P. Thayer, A.L. Warshaw, C. Fernández-del Castillo. 2005. Pancreatology 5(1):37-43.
“…Our study demonstrates degradation and inactivation of TNFalpha by pancreatic proteases...”
Protease specifically regulate cytokines, such as TNF, as the next study confirms.
Neutrophil serine proteases fine-tune the inflammatory response.
Pham, C.T.N. 2008. Int J Biochem Cell Biol. 40(6-7):1317-1333.
“…However, studies over the past several years indicate that neutrophil serine proteases may also be key regulators of the inflammatory response. Neutrophil serine proteases specifically process and release chemokines, cytokines, and growth factors, thus modulating their biological activity. In addition, neutrophil serine proteases activate and shed specific cell surface receptors, which can ultimately prolong or terminate cytokine-induced responses…”
Any illness associated with a lack of protease will have elevated levels of TNF. For instance, I have posted studies on the thread "Some Interesting Connections" on the association to a lack of protease to Alzheimer's disease, hypothyroidism, Sjogrens, lupus, RA, etc.
Alzheimer’s disease (AD) patients have “significantly elevated levels of TNF”, as was stated in the following study.
Elevated circulating tumor necrosis factor levels in alzheimer’s disease.
Fillit, H., W.H. Ding, L. Buee, J. Kalman, L. Altstiel, B. Lawlor, G. Wolf-Klein. 1991. Neurosci Lett. 129(2):318-20.
“…Significantly elevated levels of TNF were found in AD sera compared to controls.”
Tumor necrosis factor is elevated in patients with hypothyroidism and Sjögren’s syndrome as well. In the study entitled “Serum concentrations of tumor necrosis factor-alpha (TNF-a) and soluble TNF-a receptor p55 in patients with hypothyroidism and hyperthyroidism before and after normalization of thyroid function” researchers found that patients with hypothyroidism had significantly higher levels of TNF than those found in controls (Diez, 2002).
In the study entitled “Tumor necrosis factor-alpha in tears of patients with Sjögren’s syndrome” researchers discovered TNF in the tears of patients with Sjögren’s syndrome, but did not detect TNF in the tears of normal controls (Oshida, 2004). The researchers concluded, “TNF-alpha was detected in the tears of patients with SS, and tear TNF-alpha levels showed a significant correlation with the grade of corneal epithelial damage, suggesting that TNF-alpha is a potent mediator in keratoconjunctivitis sicca.”
In the next study the researchers concluded their results suggest a central role of TNF in the initiation and progression of autoimmune destruction of salivary glands.
Inhibition of submandibular and lacrimal gland infiltration in nonobese diabetic mice by transgenic expression of soluble TNF-receptor p55.
Hunger, R.E., S. Müller, J.A. Laissue, M.W. Hess, C. Carnaud, I. Garcia, and C. Mueller. 1996. J Clin Invest. 98(4): 954–961.
“Direct evidence for an instrumental role of TNF-alpha in initiation and progression of submandibular and lacrimal gland infiltration is provided …These data suggest a central role of TNF-alpha in the initiation and progression of autoimmune tissue destruction of salivary glands and indicate beneficial effects of soluble TNF receptors in the treatment of organ-specific autoimmune diseases.”
TNF appears to play a major pro-inflammatory role in SLE also,” as was stated in the study entitled “The role of tumor necrosis factor-alpha in systemic lupus erythematosus” (Aringer, 2008).
Due to a lack of protease, elevated tumor necrosis factor also plays a role in diseases not thought of as being associated with inflammation, such as chronic fatigue syndrome (CFS) and fibromyalgia. Patients with fibromyalgia were found to have elevated levels of TNF in the study entitled “Cytokine patterns in fibromyalgia and their correlation with clinical manifestations” (Bazzichi, 2007).
The following study identified elevated tumor necrosis factor in chronic fatigue syndrome.
Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression.
Patarca, R., N.G. Kilmas, S. Lugtendorf, M. Antoni, M.A. Fletcher. 1994. Clin Infect Dis. 18(Suppl.1):S147-53.
“Among a group of 70 individuals who met the criteria established by the Centers for Disease Control and Prevention (Atlanta) for chronic fatigue syndrome (CFS), 12%-28% had serum levels exceeding 95% of control values for tumor necrosis factor (TNF) alpha…”
So, I don't think it is bad to have TNF, I just think it is bad to have elevated levels of TNF.