Inflammatory Bowel Disease Treatment

Abstract: Inflammatory bowel diseases(IBD) mainly include ulcerative colitis(UC) and Crohn's disease(CD), affecting about six to eight million people around the world. Features of IBD include chronicity, progressiveness and recurrence, obviously affecting patients' quality of life and increasing medical expense. IBD is usually considered to be derived from abnormal immune response of genetic suscept to microorganism. However, the pathogenesis still remains unclear.

Keywords: Inflammatory bowel disease, Autoimmune diseases, Immune system disorders, Immunotherapy

1. Inflammatory Bowel Disease Symptoms

Common IBD symptoms include:
(1) Diarrhea and bloody mucus in stool; Increased frequency of defecation easily induces electrolytedisturbance;
(2) Recurrent abdominal pain usually appears in lower abdomen or belly button, relevant to inflammatory degree;
(3) Malnutrition and emaciation are induced by malabsorption and loss of appetite;
(4) Hypodynamia, anxiety or depression affects mental state and quality of life;
(5) Crohn's disease is associated with perianal lesions, abscess;
(6) Extraintestinal manifestations in skin, joint and eye.

2. Immunologic Pathogenesis of IBD

Roles of various cytokine in IBD are important, e.g. IL-22, IL-6, IL-12/IL-23, IL-17, IL-10, IL-1β, TNF, TL1A family. IL-22 is secreted by Th22, Th17 and Th1 cell, promoting intestinal tissue repair via inhibition of enteric pathogen. The expression in small intestine is induced by microbiota signal. IL-6 is mainly derived from macrophage and dendritic cell, and related to disease activity. The activated gp130 positive promotes transcription of anti-apoptotic gene. IL-12 and IL-23 drive pathogenic T cell response, promoting Th1 cell differentiation and Th17 cell reaction. IL-17 affects pathogenesis of IBD via Th17 cell. Dysfunction of IL-10 as key immunosuppressive cytokine is related to idiopathic colitis. IL-1β acts on IBD inflammatory process with other pro-inflammatory factors. TNF and the family member TL1A are pro-inflammatory cytokines. Anti TNF-α treatment is one of the important IBD therapies. Besides, immune cell migration(especially T cell migration) is very significant for IBD, involved in roles of various molecules(like integrin, selectin and chemokine). Different therapies against these molecules provide new treatment methods for IBD patients.

3. IBD Immunotherapy

Currently, FDA has approved 7 biological reagents for IBD treatment. Meanwhile, many innovative drug candidates for IBD have been in clinical trials, providing more potential choices for patients.

Various targeted drugs have been applied in IBD treatment. Anti TNF-α reagents have been approved for treating Crohn's disease(CD) and ulcerative colitis(UC), e.g. infliximab, adalimumab, golimumab and certolizumab pegol etc. But some patients don't respond or curative effect decreases with time. Drugs targeting IL-12/IL-23 have already shown better curative effect, e.g. ustekinumab. Antibodies against IL-23p19 are still in clinical trials, e.g. risankizumab. JAK inhibitors like tofacitinib has been approved for UC treatment. Besides, biological reagents targeting cell adhesion molecules can efficiently inhibit migration of T cell to intestine, e.g. vedolizumab, natalizumab. Therapeutic strategies for NLRP3 inflammasome are investigated. Important roles of NLRP3 in IBD inflammatory response show its potential in future treatment.

In recent years, obvious advances in immunologic pathogenesis research of IBD are achieved, providing new therapeutic methods. In the future, treatments for specific gene sites may be a breakthrough. Meanwhile, new antibodies, combination therapy and multiple-factor blockers are expected to improve therapeutic effects for IBD patients.

REFERENCES

[1]miRNA-loaded biomimetic nanoparticles orchestrate gut microbe to ameliorate inflammatory bowel disease, PMID: 41270175.
[2]Microbiota in inflammatory bowel disease: mechanisms of disease and therapeutic opportunities, PMID: 40065181.