Tag: immunomodulators

Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut

Abstract:

Certain therapeutic microbes, including Bifidobacteria infantis (B. infantis) 35624 exert beneficial immunoregulatory effects by mimicking commensal-immune interactions; however, the value of these effects in patients with non-gastrointestinal inflammatory conditions remains unclear.

In this study, we assessed the impact of oral administration of B. infantis 35624, for 6‒8 weeks on inflammatory biomarker and plasma cytokine levels in patients with ulcerative colitis (UC) (n = 22), chronic fatigue syndrome (CFS) (n = 48) and psoriasis (n = 26) in three separate randomized, double-blind, placebo-controlled interventions. Additionally, the effect of B. infantis 35624 on immunological biomarkers in healthy subjects (n = 22) was assessed.

At baseline, both gastrointestinal (UC) and non-gastrointestinal (CFS and psoriasis) patients had significantly increased plasma levels of C-reactive protein (CRP) and the pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) compared with healthy volunteers. B. infantis 35624 feeding resulted in reduced plasma CRP levels in all three inflammatory disorders compared with placebo.

Interestingly, plasma TNF-α was reduced in CFS and psoriasis while IL-6 was reduced in UC and CFS. Furthermore, in healthy subjects, LPS-stimulated TNF-α and IL-6 secretion by peripheral blood mononuclear cells (PBMCs) was significantly reduced in the B. infantis 35624-treated groups compared with placebo following eight weeks of feeding.

These results demonstrate the ability of this microbe to reduce systemic pro-inflammatory biomarkers in both gastrointestinal and non-gastrointestinal conditions. In conclusion, these data show that the immunomodulatory effects of the microbiota in humans are not limited to the mucosal immune system but extend to the systemic immune system.

 

Source: Groeger D, O’Mahony L, Murphy EF, Bourke JF, Dinan TG, Kiely B, Shanahan F, Quigley EM. Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut. Gut Microbes. 2013 Jul-Aug;4(4):325-39. doi: 10.4161/gmic.25487. Epub 2013 Jun 21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744517/ (Full article)

 

TLR3 agonists as immunotherapeutic agents

The interaction of innate and adaptive immune responses is extremely complex and just beginning to be understood in detail. The tendency for biomedical research to establish reproducible models, cell systems and receptor pathways, and then to focus on these systems can sometimes result in opportunity that is not appreciated. The Toll-like receptor (TLR)3 pathway as a therapeutic target falls into this category. There is an immense body of data that has been developed for more than 40 years; all of which is highly relevant to the TLR3 story and yet most of which predates the elucidation of the TLR pathways. A new recognition of TLR3, its unique properties that distinguish it from other TLR pathways, the specificity of relevant and long-available TLR agonists, and new studies of this biology utilizing modern assay methodology suggest that this target may be especially valuable as an adjunct to multiple immunotherapy strategies currently in use or in development.

You can read the rest of this article here: http://www.futuremedicine.com/doi/full/10.2217/imt.10.8 (Full article)

 

Source: Christopher F Nicodemus and Jonathan S Berek. TLR3 agonists as immunotherapeutic agents. Immunotherapy, March 2010 ,Vol. 2, No. 2, Pages 137-140 , DOI 10.2217/imt.10.8 (doi:10.2217/imt.10.8)  http://www.futuremedicine.com/doi/full/10.2217/imt.10.8 (Full article)

Clinical impact of B-cell depletion with the anti-CD20 antibody rituximab in chronic fatigue syndrome: a preliminary case series

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a disease of unknown aetiology. A patient with CFS had unexpected, marked recovery of CFS symptoms lasting for five months during and after cytotoxic chemotherapy for Hodgkin’s disease. We reasoned that the transient CFS recovery was related to methotrexate treatment, which induces immunomodulation in part through B-cell depletion.

METHODS: In a case series, this patient and two additional CFS patients were B-cell depleted by infusion of the monoclonal anti-CD20 antibody rituximab.

RESULTS: All three had improvement of all CFS symptoms. Patients 1 and 2 had major amelioration from 6 weeks after intervention, patient 3 slight improvement from the same time, but then improved markedly from 26 weeks after intervention. The symptomatic effect lasted until weeks 16, 18 and 44, respectively. At relapse, all were retreated with a single (patient 1) or double rituximab infusion (patients 2 and 3). Again, all three had marked symptom improvement, mimicking their first response. After new symptom recurrence, patients 1 and 2 were given weekly oral methotrexate, patient 1 having effect also from this agent. Patients 1 and 2 were again treated for a third rituximab infusion after new relapse, again with a marked clinical benefit. No unexpected toxicity was seen.

CONCLUSION: These observations suggest that B-lymphocytes are involved in CFS pathogenesis for a subset of patients. Benefit for all CFS symptoms, the delayed symptom relief following B-cell depletion, the kinetics of relapses, and the effect also from methotrexate treatment, provide suggestive evidence that B-cells play a significant role in the ongoing clinical features, and that CFS may be amenable to therapeutic interventions aimed at modifying B-cell number and function. More systematic investigations of this therapeutic strategy, and of its biological basis, are now needed.

 

Source: Fluge Ø, Mella O. Clinical impact of B-cell depletion with the anti-CD20 antibody rituximab in chronic fatigue syndrome: a preliminary case series. BMC Neurol. 2009 Jul 1;9:28. doi: 10.1186/1471-2377-9-28. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711959/ (Full article)

 

Chronic fatigue syndrome

Abstract:

The authors followed up for a period of 1-14 years 52 patients with CFS who met the criteria outlined by Holmes. The group comprised 10 men and 42 women. In 15% of these patients after a mean period of 5.5 years thyroiditis was diagnosed. Complete recovery was recorded in 20%, improvement in 32% of the patients, on average after 7 years. In the course of treatment mainly immunomodulating preparations were used. Indication of these drugs was individual based on immunological examinations. The success was only partial. The clinical condition of the patients did not correlate with serological findings of IgM, IgA and IgG antibodies against VCA nor with antibodies against EA of the EBV virus.

 

Source: Fucíková T, Petanová J. Chronic fatigue syndrome. Vnitr Lek. 1993 Oct;39(10):995-1002. [Article in Czech] http://www.ncbi.nlm.nih.gov/pubmed/8236872

 

Chronic fatigue syndrome: a critical review

Abstract:

The term “chronic fatigue syndrome” (CFS) applies to a condition of unknown aetiology characterized clinically by an association of subjective symptoms, the most constant being an invalidating tiredness. The diagnostic criteria in current use do not permit to isolate an homogeneous subgroup among patients consulting for chronic asthenia.

In the present state of research no infectious or immunological cause has been demonstrated conclusively, although a persistent enterovirus or herpesvirus type 6 infection or a state of chronic immune activation seem to play a role in some cases. Patients who fulfill the criteria of CFS present with psychiatric overmorbidity, essentially depressive, and in 50% of the cases with the mental disorders preceding CFS. The various theoretical models linking CFS to psychopathology are discussed, and finally the syndrome is regarded as a social construction reproducing or renovating the neurasthenia of the late 19th century.

There is no specific treatment of CFS, but antidepressants, cognitive-behavioural therapy and perhaps certain immuno-modulators can be useful. The future lines of research should endeavour to isolate a subgroup of patients with prolonged asthenia after a recognized episode of infection and to identify the immunological, psychological and behavioral characteristics of this particular group as well as their reciprocal interactions.

 

Source: Cathébras P, Bouchou K, Charmion S, Rousset H. Chronic fatigue syndrome: a critical review. Rev Med Interne. 1993 Apr;14(4):233-42. [Article in French] http://www.ncbi.nlm.nih.gov/pubmed/8378654