Immune modulation after long-term karate practice

Introduction: Karate is a Japanese martial arts system which traces its roots back to China, and is nowadays widely popular both as a method of self-defense, as well as a discipline with potential physical and psychological benefits. However, karate has been scarcely investigated from a psychobiological perspective, and its effects on the immune system remain virtually unknown. Therefore, we designed the present study with the aim of analyzing the effects of several years of regular karate practice on different immune parameters. Methods: 27 healthy volunteer subjects participated in the study, 15 being allocated to the experimental group, and 12 to the control group. Experimental subjects were all karate players who had practiced this martial art for a minimum of three years. Blood samples for the quantification of immune parameters (leukocytes, neutrophils, monocytes, eosinophils, basophils, lymphocytes, IgG, IgA, IgM, IgE) were taken in both groups. As statistical analysis, a t-test for independent groups was performed in each dependent variable. Results: Compared to the control group, karate practitioners exhibited a significantly higher number of leukocytes, monocytes, and lymphocytes, as well as greater serum concentrations of IgG and IgM. Conclusions: Our findings show that long-term karate practice is related to a broad modulation of immune parameters, including leukocytes counts as well as immunoglobulin concentrations. This peculiar immunomodulatory profile, apart from its psychobiological relevance, may have noteworthy clinical implications. Further investigation would be necessary to fully elucidate the influence that long-term karate training can exert on the immune system.Universidad de Málaga, Campus de Excelencia Internacional Andalucía Tec

Immune Modulation as a Treatment for Abdominal Aortic Aneurysms

In the United States, over 200,000 new patients are diagnosed with abdominal aortic aneurysm (AAA) each year. Consequently, over 40,000 highly morbid aortic reconstructions are performed each year to prevent aneurysm rupture, a catastrophic event associated with near-certain mortality. No pharmaceutical currently exists to slow aneurysm growth, but a 50% reduction in diameter growth per annum could halve the number of aortic reconstructions required. Therefore, successful use of cell therapy to modulate chronic inflammation hallmark to AAA to slow diameter expansion represents a potentially paradigm-altering treatment

Immune modulation by fish kinetoplastid parasites : a role for nitric oxide

Trypanoplasma borreli and Trypanosoma carassii are kinetoplastid parasites infecting cyprinid fish. We investigated the role of nitric oxide (NO) in immune modulation during T. borreli and T. carassii infection of carp. Phagocytic cells from different organs produced NO and serum nitrate levels increased, demonstrating that T. borreli activates NO production in vivo. In contrast, T. carassii did not induce NO production in vivo and inhibited LPS-induced NO production in vitro. Production of NO was detrimental to the host as T. borreli-infected carp treated with the inducible NO synthase inhibitor aminoguanidine had a higher survival than infected control carp. This detrimental effect can be explained (in part) by the toxicity of NO to cells in vitro as NO inhibited the proliferative response of blood and spleen leukocytes. Head-kidney phagocytes were resistant to the immunosuppressive effects of NO in vitro. The NO-inducing activity of T. borreli may be an adaptation developed to ensure survival and immune evasion in the fish host. Apparently, T. carassii has adopted another strategy by deactivating specific functions of phagocytes. Both strategies may ensure long-term survival of the parasite

Tumour heterogeneity and immune-modulation.

Recent advances in sequencing technologies have revealed extensive intratumour heterogeneity (ITH) both within individual tumours and between primary and metastatic tumours for different cancer types. Such genetic diversity may have clinical implications for both cancer diagnosis and treatment with increasing evidence linking ITH and therapeutic resistance. Nonetheless, whilst limiting the activity of targeted agents, tumour genetic heterogeneity may provide a new therapeutic opportunity through generation of neo-antigens that could be recognised and targeted by the patient's own immune system in response to immune-modulatory therapies. Longitudinal genomic studies assessing tumour clonal architecture and its correlation with the underlying immune response to cancer in each particular patient are needed to follow tumour evolutionary dynamics over time and through therapy, in order to further understand the mechanisms behind drug resistance and to inform the development of new combinatorial therapeutic strategies

Immune Modulation By Amphiphilic Oligonucleotides

Immunotherapy is emerging as one of the most promising therapeutic strategies for cancer treatment in clinical practice. Immunotherapy leverages the host’s immune system to attack and kill tumor cells. Rationally-designed cancer vaccines are emerging as one of the powerful immunotherapies primarily because of the promise of inducing tumor antigen-specific immune responses. To improve immunogenicity of cancer vaccines, vaccine antigens are administered with vaccine adjuvants which can robustly activate innate immune system and subsequently lead to adaptive immune response. However, the major challenge of achieving significant therapeutic efficacy is lack of efficient targeted-delivery of vaccine components. By taking advantage of endogenous albumin, lipid modified oligonucleotides-based adjuvants can be efficiently transported to draining lymph nodes (dLNs), where a variety of immune cells reside, and subsequently activate the adaptive immune system. This “albumin-hitchhiking” strategy represented a novel and efficient way for LN-targeted delivery of biologics, improving the therapeutic efficacy in cancer vaccines. The aims of this dissertation are to further expand the scope of “albumin-hitchhiking” approach in immunomodulation. We first evaluated three representative classes of lipid modified immunostimulatory CpG ODNs. All lipo CpG ODNs considerably drained to LNs more than unmodified CpG ODNs, while they appeared to be functionally compromised in in vitro immune activation. However, administration of lipo CpG class B and C ODNs, not lipo CpG class A ODN, with protein antigen in mice led to improved antigen-specific CD8+ T cell responses and humoral responses relative to their parent compounds. We then evaluated the therapeutic efficacy of immunosuppressive ODN A151 and its lipid modified form in inhibiting TLR9-mediated immune activation. The data showed that lipo ODN A151 was preferentially internalized by cells and accumulated in LNs in a larger magnitude compared to unmodified ODN A151. More importantly, prophylactic administration of lipo ODN A151, but not unmodified ODN A 151, resulted in profound inhibition of immune responses challenged and induced with CpG-adjuvanted vaccines. Next, we investigated structure-dependent stability of lipid modified amphiphilic polymers on red blood cells (RBCs). We revealed that longer lipid chain was preferred for more stable insertion on RBCs surface ex vivo, while shorter polyethylene glycerol (PEG) spacer conjugated amphiphiles exhibited more stable retention on RBCs in vivo. Moreover, cationic amphiphiles constructed with cationic lipids resulted in significantly prolonged circulation half-life on RBCs in vivo. Finally, we discovered a novel adjuvant enhancer which improved the adjuvant activities of TLR7/8 in vitro and in vivo. We found that certain amphiphilic oligonucleotides could improve TLR7 ligand induced NF-kB activation in the presence of albumin protein. In vivo, administration of imiquimod-adjuvanted vaccine mixed with structurally optimized amphiphilic oligonucleotide-based adjuvant booster induced markedly increased frequency of antigen-specific CD 8+ T cells and production of antigen-specific IgG in mice, while the same vaccine without adjuvant booster showed no effect. Thus, lipid functionalized oligonucleotide-based adjuvants booster could greatly improve immunogenicity of subunit vaccines. Collectively, lipid functionalized oligonucleotides not only accumulate in LNs by hitchhiking endogenous albumin, but also versatilely modulate the immune responses. Amphiphilic oligonucleotides may be broadly applicable for diseases involving the immune system, where immunomodulation is needed

Mesenchymal stem cells for management of rheumatoid arthritis : immune modulation, repair or both?

The authors are grateful for support to their research from Arthritis Research UK (grants 19271, 19429, 19667, 20050, 20775) and the Medical Research Council (grant no. MR/L020211/1)Peer reviewedPostprin

Immune modulation in gene therapy studies

Summary Host immune responses play a major role in clearance of viral infections from the body, and may limit long-term expression and clinical efficacy of viral vectors. Methods to prevent these immune responses may also increase the risk for infections, recombination with wild type virus and affect biodistribution, persistence, shedding and transmission. The study described in this report was initiated to assess possible environmental risks associated with the use of immune modulation in combination with gene therapy and set up as a literature study, by performing PubMed searches for certain keywords, by interviewing experts and by attending selected meetings. Lack of availability of clinical data combining gene therapy and immune modulation and limited animal data warranted additional exploration of relevant non-gene therapy studies from closely related fields such as stem cell and organ transplantation, and vaccination studies with live attenuated vaccines. ...... Finally, we propose the use of a checklist to assess current environmental risks in the use of immune modulation during gene therapy. This report is expected to provide guidance to risk assessors and regulatory officers as well as to applicants for a gene therapy licence