The information on this site is for educational purposes only. Dr. Weber is not a medical doctor and does not advocate the use of dehydroepiandrosterone (DHEA) to treat any form of multiple sclerosis. You should consult with your physician before starting any form of treatment. At this time there is insufficient scientific evidence to establish whether or not DHEA is an effective therapeutic agent against any form of multiple sclerosis. Persons diagnosed with multiple sclerosis should consult with their physician before using DHEA as a dietary supplement.

Interferon beta-2 (Interleukin-6) suppression: a possible treatment strategy for Primary Progressive Multiple Sclerosis?

by Brett Curtis Weber, Ph.D.
Published March 1999

Literature review:

Administering a single cytokine by injection has been a treatment strategy for relapsing remitting and secondary progressive multiple sclerosis (MS). For example, injection of the cytokine interferon beta-1a (Avonex) or interferon beta-1b (Betaseron) reduced frequency of exacerbation in relapsing-remitting MS and may slow progression in secondary progressive MS (Knobler 1993; Paty 1993; Jacobs 1995; Polman 1995, ESG 1998). In contrast, the progression of primary progressive MS in some patients was not slowed, but seemed accelerated by interferon beta-1a (Avonex) or interferon beta-1b (Betaseron) therapy (Weber, personal observations). Barmanti and colleagues (1998) observed an “increased spasticity requiring increased antispasticity drug administration” in primary progressive patients treated with interferon beta-1b (Betaseron) and suggested further studies before interferon drugs become widely prescribed to primary progressive MS patients. Individuals with adrenoleukodystrophy, a disorder that can involve demyelination of nerve cells within the central and peripheral nervous systems, also responded poorly to interferon beta-1b (Betaseron) treatment (Korenke 1997). It is, therefore, possible that part of the pathology of primary progressive MS is dissimilar from relapsing-remitting and secondary progressive MS, and perhaps comparatively similar to adrenoleukodystrophy. At present, there is no proven effective treatment for patients with primary progressive multiple sclerosis.

Neutralizing or suppressing a single cytokine is another promising strategy in the treatment of multiple sclerosis. Transgenic mice that do not express the cytokine interferon beta-2 (also called interleukin-6) were resistant to myelin oligodendrocyte glycoprotein (MOG) induced experimental autoimmune encephalomyelitis (EAE)--an animal model for multiple sclerosis (Okuda 1998). Conversely, chronic overexpression of interferon beta-2 (IL-6) produced neuroanatomical and neurophysiological abnormalities within the murine central nervous system (CNS) similar to those observed in patients with multiple sclerosis and other neurological diseases (Woodroofe 1992). Further, the severity of the neurological syndrome observed in transgenic mice correlated with the levels of interferon beta-2 (IL-6): mice expressing higher levels of interferon beta-2 (IL-6) developed more severe neurological abnormalities than mice expressing less interferon beta-2 (IL-6) (Campbell 1993). Administration of neutralizing antibodies to interferon beta-2 (IL-6) had a "disease-reducing effect" on mice with EAE (Gijbels 1995). Similarly, in patients with an unspecified type of multiple sclerosis, interferon beta-2 (IL-6) levels in sera and cerebrospinal fluid (CSF) were significantly higher than normal controls (Shimada 1993). Consequently, overexpression of interferon beta-2 (IL-6) in human patients may trigger part of the pathology of multiple sclerosis. Brod and colleagues (1996) observed that treatment with interferon beta-1b (Betaseron) further increased interferon beta-2 (IL-6) secretion in patients with stable relapsing-remitting MS. Brod and colleagues (1996) suggest that increased interferon beta-2 (IL-6) secretion during interferon beta-1b (Betaseron) treatment could potentially counteract the beneficial immunomodulatory effects of interferon beta-1b (Betaseron).

Though interferon beta-1b (Betaseron) increased interferon beta-2 (IL-6) secretion in relapsing-remitting MS, most patients experienced fewer exacerbations (Knobler 1993; Paty 1993; Brod 1996). In contrast, interferon beta-1b (Betaseron) was not well tolerated by primary progressive patients, and may accelerate the progression of the disease (Barmanti 1998; Weber, personal observations). It is conceivable, therefore, that primary progressive MS patients are more vulnerable to elevated interferon beta-2 (IL-6) sera and CSF levels than relapsing-remitting and secondary progressive patients, and that suppression of this cytokine could slow disease progression. Since there is no current proven effective treatment for primary progressive multiple sclerosis, it is imperative that interferon beta-2 (IL-6) suppression be considered by the scientific community as a possible treatment for primary progressive multiple sclerosis.

Dehydroepiandrosterone (DHEA) is an androgenic steroidal hormone produced by the adrenal gland that has a natural immunomodulatory effect on interferon beta-2 (IL-6) (Straub 1998). Serum DHEA and DHEA sulfate levels were negatively correlated with serum interferon beta-2 (IL-6) levels in humans (Straub 1998). DHEA also inhibited interferon beta-2 (IL-6) secretion from human mononuclear cells in vitro (Straub 1998). Accordingly, DHEA supplementation would provide a very viable and inexpensive treatment option for suppressing systemic levels of interferon beta-2 (IL-6). In a mixed group of relapsing-remitting and chronic progressive multiple sclerosis patients, DHEA-S levels tended to be low when compared to an accepted reference range based on age and sex (Dharmananda 1997). In healthy individuals, serum DHEA levels tended to decrease with age, whereas interferon beta-2 (IL-6) levels tended to increase (James 1997; Straub 1998). Since DHEA is a naturally occurring molecule found within the body, maintaining DHEA serum levels within a healthy young adult reference range may be a very logical and extremely safe treatment option for individuals with primary progressive MS.

For a molecular theory on how acute emotional stress may affect the course of PPMS, please visit my next section on Psychoneuroimmunology (PNI).

Works Cited:

Barmanti P; Sessa E; Rifici C; D'Aleo G; Florida D; Di Bella P; Lublin F: Enhanced spasticity in primary progressive MS patients treated with interferon beta-1b; Neurology 1998 Dec; 51(6):1720-3

Brod SA; Marshall GD Jr; Henninger EM; Sriram S; Khan M; Wolinsky JS: Interferon-beta 1b treatment decreases tumor necrosis factor-alpha and increseases interkeukin-6 production in multiple sclerosis; Neurology 1996 Jun; 46(6):1633-8

Calabrese VP: DHEA in multiple sclerosis: positive effects on fatigue syndrome in a non-randomized study; in The Biological Role of DHEA by Kalimi M; Regelson W;1990 New York Walter, De Gruyter; 95-100

Campbell IL; Abraham CR; Masliah E; Kemper P; Inglis JD; Oldstone MB; Mucke L: Neurologic disease induced in transgenic mice by cerebral overexpression on interleukin 6; Proc Natl Acad Sci USA 1993 Nov 1; 90(21):10061-10065

Dharmanada S: Evaluation of DHEA levels in multiple sclerosis; Institute for Traditional Medicine, Portland Oregon 1997; ITM Online (visited Feb. 17, 1999) Internet Publication

Embry AF: Multiple sclerosis: probable cause and best-bet treatment; International MS Support Foundation, P.O. Box 90154, Tucson, Arizona; IMSSF Online (visited Feb. 17, 1999) Internet Publication

European Study Group on interferon beta-1b in secondary progressive MS: Placebo-controlled multicentre randomised trial of interferon beta-1b in treatment of secondary progressive multiple sclerosis; Lancet 1998 Nov 7;352(9139):1491-7

Gijbels K; Brocke S; Abrams JS; Steinman L: Administration of neutralizing antibodies to interleukin-6 (IL-6) reduces experimental autoimmune encephalomyelitis and is associated with elevated levels of IL-6 bioactivity in the central nervous system and circulation; Mol Med 1995 Nov; 1(7):795-805

Jacobs LD; Cookfair DL; Rudick RA; Herndon RM; Richert JR; Salazar AM; Fischer JS; Goodkin DE; Granger CV; Simon JH: A phase III trial on intramuscular recombinant interferon beta treatment for exacerbating-remitting multiple sclerosis: design and conduct of study and baseline characteristics of patients; Mult Scler 1995 Jun; 1(2):118-35

James K; Premchand N; Skibinska, A; Skibinski G; Nicol M; Mason J: I IL-6, DHEA and the aging process; Mech Ageing Dev 1997 Feb; 93(1-3):15-24

Knobler RL; Greenstein JI; Johnson KP; Lublin FD; Panitch HS; Conway K; Grant-Gorsen SV; Muldoon J; Marcus SG; Wallenberg JC: Systemic recombinant human interferon-beta treatment of relapsing-remitting multiple sclerosis: pilot study analysis and six-year follow-up; J Interferon Res 1993 Oct; 13(5):333-40

Korenke GC; Christen HJ; Kruse B; Hunneman DH; Hanefeld F: Progression of X-linked adrenoleukodystrophy under interferon-beta therapy; J Inherit Metab Dis 1997 Mar; 20(1):59-66

MacDougall R: My fight against multiple sclerosis; Regenics Inc, Mansfield, Ohio 1980; Reprint International MS Support Foundation, P.O. Box 90154, Tucson, Arizona; IMSSF Online (visited Feb. 17, 1999) <> Internet Publicatio

Okuda Y; Sakoda S; Bernard CC; Fujimura H; Sacki Y; Kishimoto T; Yanagihara T: IL-6-deficient mice are resistant to the induction of experimental autoimmune encephalomyelitis provoked by myelin oligodendrocyte glycoprotein; Int Immunol 1998 May; 10(5):703-8

Paty DW; Li DK: Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. II. MRI analysis results of a multicenter, randomized, double-blind, placebo-controlled trial; Neurology 1993 Apr; 43(4):662-7

Polman CH; Dahlke F; Thompson AJ; Ghazi M; Kappos L; Miltenburger C;

Pozilli C: Interferon beta-1b in secondary progressive multiple sclerosis--outline of clinical trial; Mult Scler 1995; 1 Suppl 1:S51-4

Roberts E; Fauble T.J: Oral DHEA in multiple sclerosis, open study; in The Biological Role of DHEA by Kalimi M; Regelson W; 1990 New York Walter, De Gruyter; 81-93

Shimada K; Koh CS; Yanagisawa N: Detection of interleukin-6 in serum and cerebrospinal fluid of patients with neuroimmunological diseases; Arerugi 1993 Aug; 42(8):934-40

Somers, W., Stahl, M., Seehra, J. S.: 1.9 A crystal structure of interleukin 6: implications for a novel mode of receptor dimerization and signaling. EMBO J 1997; 16 pp. 989

Straub R H; Konecna L; Hrach S; Rothe G; Kreutz M; Scholmerich J; Falk W; Lang B: Serum dehydroepiandrosterone (DHEA) and DHEA sulfate are negatively correlated with serum interleukin-6 (IL-6), and DHEA inhibits IL-6 secretion from mononuclear cells in man in vitro: possible link between endocrinosenescence and immunosenescence; J Clin Endocrinol Metab 1998 Jun; 83(6):2012-7

Swank RL; Dugan BB: Effect of low saturated fat diet in early and late cases of multiple sclerosis; Lancet 1990 336:37-39.

Swank RL; Dugan BB: The Multiple Sclerosis Diet Book; 1987 Doubleday, Garden City, New York

Weber, B: Personal observations; August-October 1998, self-observation while being treated for primary progressive multiple sclerosis using interferon beta-1b (Betaseron); October-February 1998, communication through the Internet with several primary progressive multiple sclerosis patients who were once treated with interferon beta-1b (Betaseron) and/or interferon beta-1a (Avonex); Target Research, 1300 Cecil B. Moore Ave, Philadelphia, Pennsylvania

Woodroofe C; Muller W; Ruther U: Long-term consequence of interleukin-6 overexpression in transgenic mice; DNA Cell Biol 1992 Oct; 11(8):587-92


Recent Publications of Interest


J Immunol 2001 Dec 15;167(12):7094-101

Administration of dehydroepiandrosterone suppresses experimental allergic encephalomyelitis in SJL/J mice.

Du C, Khalil MW, Sriram S.

Department of Neurology, Multiple Sclerosis Research Center, Vanderbilt University Medical Center, Nashville, TN 37212, USA.

Experimental allergic encephalomyelitis (EAE) is a Th1-mediated inflammatory demyelinating disease in the CNS, an animal model of multiple sclerosis. We have examined the effect of dehydroepiandrosterone (DHEA) on the development of EAE in mice. The addition of DHEA to cultures of myelin basic protein-primed splenocytes resulted in a significant decrease in T cell proliferation and secretion of (pro)inflammatory cytokines (IFN-gamma, IL-12 p40, and TNF-alpha) and NO in response to myelin basic protein. These effects were associated with a decrease in activation and translocation of NF-kappaB. In vivo administration of DHEA significantly reduced the severity and incidence of acute EAE, along with a decrease in demyelination/inflammation and expressions of (pro)inflammatory cytokines in the CNS. These studies suggest that DHEA has potent anti-inflammatory properties, which at least are in part mediated by its inhibition of NF-kappaB activation.

PMID: 11739531 [PubMed - indexed for MEDLINE]


Neuroendocrinology 1999 Dec;70(6):431-8

Dehydroepiandrosterone response to the adrenocorticotropin test and the combined dexamethasone and corticotropin-releasing hormone test in patients with multiple sclerosis.

Kumpfel T, Then Bergh F, Friess E, Uhr M, Yassouridis A, Trenkwalder C, Holsboer F.

Max Planck Institute of Psychiatry, Munich, Germany.

Basic and clinical research suggest that disturbed neuroendocrine function may be involved in the pathogenesis and course of autoimmune diseases including multiple sclerosis (MS). Dehydroepiandrosterone (DHEA) in this connection is of particular interest as it appears to have effects on the immune system. Moreover, DHEA levels are decreased in chronic inflammatory diseases. To further investigate the role of DHEA in MS, we administered the adrenocorticotropin (ACTH) stimulation test and the combined dexamethasone and corticotropin-releasing hormone (DEX-CRH) test to 24 patients with active MS (13 women, 11 men; age 39 +/- 2 years, mean +/- SEM; Expanded Disability Status Scale, EDSS score 4.4 +/- 0. 4, mean +/- SEM; 12 with acute relapse, 12 with chronic progression) and to 18 healthy controls matched for age and sex (8 women, 10 men; age 37 +/- 3 years). There were no statistically significant differences in the plasma cortisol response to ACTH between any groups. In the DEX-CRH test, plasma cortisol concentrations showed higher values before (DEX-pretreated) and after CRH stimulation in the MS patients than in the controls (AUC(cortisol) 738.3 +/- 154.5 vs. 295.7 +/- 55.8; p < 0.05), this finding was more pronounced in chronic progressive patients. DHEA concentrations were decreased in MS patients (AUC (DHEA) 14.4 +/- 1.6 vs. 23 +/- 2.4; p < 0.05) and cortisol/DHEA ratios were increased in the patients compared to the controls (p < 0.05). There was a positive correlation between the EDSS score and maximum cortisol/DHEA ratio (r = 0.45; p = 0.031). As with the hypothalamic-pituitary-adrenal axis system, our results suggest a dysfunction in the DHEA secretion in patients with MS. Copyright 1999 S. Karger AG, Basel.

PMID: 10657736 [PubMed - indexed for MEDLINE]




Interferon beta-2 (Interleukin-6)




Dehydroepiandrosterone (DHEA)



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