71(immunomodujmpr-11-1401

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Journal of Medicinal Plants Research Vol. 6(7), pp. 1100-1105, 23 February, 2012Available online at http://www.academicjournals.org/JMPRDOI: 10.5897/JMPR11.1401ISSN 1996-0875 2012 Academic Journals

Review

Autoimmune diseases and immunomodulant plant

M.M. Akram1, M. Saim Jamil1, Zahid Mehmood2, Khan Usmanghani1, Iqbal Azhar4,Muhammad Akram5, H. M. Asif3and Umar Iqbal1

1Shifa ul Mulk Memorial Hospital, Hamdard University, Karachi, Pakistan.

2Department of Chemistry and Biochemistry, University of Agriculture, Faisalabad, Pakistan.

3Department of Pharmacy, The Islamia University of Bahawalpur, Pakistan.

4Department of Pharmacognosy, University of Karachi, Pakistan.

5Department of Pharmacy, University of Sargodha, Pakistan.

Accepted 4 November, 2011

The immune system in general responds appropriately to the presence of foreign antigens. Bodyimmune system protects the body against invading organisms. In an autoimmune disease, immunesystem attacks healthy cells in body by mistake. Autoimmune diseases can affect many parts of thebody. Various plants are used to strengthen the immunity due to their immunomodulatory activities. Inthis article, autoimmune diseases, description of autoimmune diseases, and plants used asimmunomodulant agent has given.

Key words:Autoimmune diseases, immunomodulatory activity, medicinal plants, research study.

INTRODUCTION

Autoimmune disorders are disorders in immuneregulation resulting in antibody or cell mediated immunityagainst the hosts own tissues (Table 1). Autoimmunedisorders may or may not result in injury to the host.Autoimmune disorders are disorders in which personsare normally unresponsive to self antigens due totolerance; however, B-cell clones do exist in persons withidiotypes reacting with self antigens. Autoimmunediseases include systemic lupus erythematosis (Ruiz-Irastorza, 2010; Hahn et al., 2008), primary centralnervous system (CNS) vasculitis, rasmussen's

encephalitis, autoimmune peri-pheral neuropathy,autoimmune cerebellar degeneration, autoimmunethrombocytopenia (Segal et al., 2006), gait ataxia withlate age onset polyneuropathy, stiff person syndrome,chronic inflammatory demyelinating poly-neuropathy,myasthenia gravis and multiple sclerosis. Hashimotosthyroiditis is a chronic autoimmune disease characterizedby immune destruction of the thyroid gland andhypothyroidism. Graves disease is autoimmune diseasecharacterized by production of immunoglobulin G (IgG)

*Corresponding author. E-mail: [email protected]: 92 021 6440083. Fax: 92 021 6440079.

auto-antibodies to the thyroid stimulating hormone (TSH)receptor. Addisons disease occurs due to destruction ofadrenal cortex leading to a deficiency of glucocorticoids,mineralocorticoids and androgens. Rheumatoid arthritis(RA) is a systemic chronic and inflammatory diseasecharacterized by progressive arthritis, production ofrheumatoid factor and extra-articular manifestation. It isthought to be caused by an autoimmune reactiontriggered by an infectious agent in a geneticallysusceptible individual (Meroni et al., 2010; Fritzler, 2011).Myasthenia gravis is an autoimmune disease

characterized by autoantibodies against theneuromuscular junction, resulting in muscular weakness.Vitiligo is characterized by irregular, completelydepigmented patches. It may affect any race. Insulindependent diabetes mellitus is thought to be caused byan autoimmune reaction triggered by an infection(Coxsakie B virus) in a genetically susceptible individual.It represents 10% of cases of diabetes. It affects childrenand adolescents usually younger than 20. Asparagusracemosus have also shown immunopotentiating effectsin cyclophasphamide treated mouse with asceticsarcoma (Diwanay et al., 2004). Kalita and Dutta (1999)reported that maternal antibody was persistently found insera samples tested against ND virus during the firstweek of age in broilers. This was attributed to transfer of


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Table 1. Autoimmune classification.

Disease Antibody against

Juvenile insulin-dependent diabetes Pancreatic islet cellsPernicious anemia Gastric parietal cells

Addison's disease Adrenal cells

Idiopathic hypoparathyroidism Parathyroid cells

Autoimmune hemolytic anemia Erythrocytes

Idiopathic thrombocytopenic purpura Platelets

Idiopathic neutropenia Neutrophils

Vitiligo Melanocytes

Chronic active hepatitis Nuclei of hepatocytes

Goodpasture's syndrome Basement membranes

Rheumatoid arthritis Gamma globulin, virus-related antigens

Sjogren's syndrome Nuclei and centromeres

Systemic lupus erythematosus Nuclei, DNA, RNA, erythrocytes, etc.Myasthenia gravis Acetylcholine receptors

Graves disease Thyroid-stimulating hormone receptor

Thyroiditis Thyroid

Insulin-resistant diabetes Insulin receptor

Asthma Beta-2 adrenergic receptors

natural passive immunity in young chicks asdemonstrated by Hellar (1975).

EXPLANATORY THEORIES FOR AUTOIMMUNEDISORDERS

1. Microbial antigens cross reacting with host tissuesinduce an immune response against self,2. Host antigen previously sequestered from fetaltolerance-inducing mechanism are released and becomeimmunogenic,3. Alteration of host molecules, exposing new antigenicdeterminants unavailable at the time of induction of fetaltolerance,4. Attachment of foreign hapten to self molecule, forminga hapten carrier complex,5. Depletion of suppressor cells.

SYSTEMIC AUTOIMMUNE DISORDERS

1. Systemic lupus erythematosis,2. Rheumatoid arthritis,3. Sjogrens syndrome,4. Polyarteritis nodosa.

ORGAN SPECIFIC AUTOIMMUNE DISORDERS

Blood

1. Autoantibodies reacting with blood cells,

2. Malignant transformation of a single plasma cell clone

(multiple myeloma).

Central nervous system

1. Allergic encephalitis,2. Multiple sclerosis,3. Myasthenia gravis.

Endocrine

1. Chronic thyroiditis,2. Graves disease,3. Diabetes mellitus.

Gastrointestinal tract

1. Pernicious anemia,2. Ulcerative colitis,3. Crohn disease,4. Chronic active hepatitis.

DISEASES INVOLVING PRIMARILY ONE TYPE OFCELL OR ORGAN

Myasthenia gravis

This acquired condition is characterized by weaknessand fatigability of proximal limb, ocular and bulbarmuscles. The heart is not involved. The cause is un-known. IgG antibodies to acetylcholine and acetylcholine

receptor proteins are found. Immune complexes (IgG and


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complement) are deposited at the postsynaptic mem-branes causing interference with and latter destruction ofthe acetylcholine receptor. The prevalence is about 4 in

100,000. It is twice as common in women as in men, witha peak incidence around the age of 30 years.

Occurrence

It occurs in one of 20, 000 persons.

Causes

It is caused by antibodies directed against the ach-receptors of the muscle fibers of sarcolemma. Theantibodies are bind to receptors and hinder theattachment of ach to the receptors. As the disease

progresses, more neuromascular junctions becomeaffected.

Clinical features

This disease is more common in females between theages of 20 to 50 years. The muscles of the face and neckare mostly involved. Initial symptoms include a weaknessof the eye muscles and difficulty in swallowing. Later, theindividual has difficulty in chewing and talking. Eventually,muscles of the limbs may become involved. Death mayresult from the paralysis of respiratorymuscles.

Treatment

Anticholinesterase drugs such as neostigmine andpyriodostigmine derivates of physostigmine are advisedto be used.

Antibodies

These are substance made in response to antigenicstimuli. They are found in plasma and are developed fromsmall lymphocytes.

Sites of antibodies production central lymphoidsystem

These are lymphoid tissue of the thymus gastroinal tract(peyers patches, tonsils, appendix).

Peripheral lymphoid organs

Lymph nodes and spleen have lymphocytes and plasmacells.

Formation of antibodies by plasma cell

All Ig are made and secreted actively by plasma

cells(Dormant B- lymphocytes in lymphoid tissue). Eachplasma cell makes 2000 molecules of antibodies(gamma-globlins).

Production of antibodies

Antigens stimulate proliferation of lymphoid cells,resulting in the production of antibodies.

Nature of antibodies

These are gamma-globulins or 1 g found free in serumand on the surface of lymphocytes. In plasma cells, theyare found inside the cells.

Major functions of antibodies: They neutralize thetoxins viruses, and also opsonize bacteria, making themeasier to phagocytize.

Concentration (normally): It isnormally 1.6 gm/100 mlof blood.

Molecular weight: It is between 150,000 to 900,000

(unit)structures of a typical 1g molecule four polypeptidechains.

Two heavy chains: Molecular weight, 20,000 (unit);Each chain has 450 amino acids.

Major groups: They are1Gg, 1Gm and 1gA.

Minor groups: They are 1 gE, 1 gD and 1 gD.

Gravess disease

Graves disease accounts for about 85% of allhyperthyroidism. It occurs most frequently in youngwomen, although it can occur in either sex at any age.Susceptibility is certainly multigenic but has beenassociated with the human leukocyte antigen (HLA)-DR3haplotype in the major histocompatibility complex (MHC)locus. It is generally characterized by hyperthyroidism

and diffuse thyroid enlarement and the presence ofcirculating antibodies directed against the TSH receptoron the membrane of the thyroid gland. Three types ofantibodies may be found.

Diabetes mellitus

This form of diabetes is immune-mediated in over 90% ofcases and idiopathic in less than 10%. The rate ofpancreatic B cell destruction is quite variable, being rapidin some individuals and slow in others. Type I diabetes isusually associated with ketosis in its untreated state. It

occurs at any age but most commonly arises in childrenand young adults with a peak incidence before school


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age and again at around puberty. It is a catabolic disorderin which circulating insulin is virtually absent, plasmaglucagon is elevated, and the pancreatic B cells fail to

respond to all insulinogenic stimuli. Exogenous insulin istherefore required to reverse the catabolic state, preventketosis, reduce the hyperglucagonemia, and reduceblood glucose.

DISEASES INVOLVING MULTIPLE ORGANS(SYSTEMIC DISEASES)

Systemic lupus erythematosus (SLE) rheumatoidarthritis (RA) and other collagen vascular diseases

These disorders feature vasculitis and collagendegeneration, plus a variety of focal inflammatory lesionsand the presence of autoantibodies against manydifferent self antigens. For example, antibodies todeoxyribonucleic acid (DNA) are found in SLE andantibodies to IgG (rheumatoid factor) occur in rheumatoidarthritis.

In Goodpastures syndrome, antibodies are formedagainst the basement membranes of the pulmonaryalveoli and the renal glomeruli. In these diseases,complement is activated by the antigen-antibodycomplexes, and neutrophils are attracted to the site.Neutrophils release various enzymes and oxygenradicals that damage the tissues. Although, in mostpatients, the immune stimulus that initiates thesedisorders is unknown, typical cases have followed

sensitization by and foreign proteins.Other diseases in this category include ankylosing

spondylitis, which is very common in people carrying theHLA-B27 gene; polymyositis- dermatomyositis, sjogrenssyndrome and Reiters syndrome.

Rheumatic fever (RF)

Rheumatic fever (RF) is a febrile disease, affectingconnective of the throat by group A beta haemolyticstrptococci. Although RF is not a communicable disease,it results from a communicable disease (streptococcal

pharyngitis). RF often leads to rheumatic heart disease(RHD) which is a crippling disease. The consequences ofRHD include continuing damage to the heart; increasingdisabilities, repeated hospitalization and premature deathusually at the age of 35 years even earlier. RHD is one ofthe most readily preventable chronic diseases.

Reiters syndrome

This syndrome consists of the triad of a seronegativereactive arthritis, non specific urethritis and conjunctivitis.The male to female ratio is 20:1 and most cases occur in

young adults. HLA-B27 is present in about 60% of cases.The diagnosis in these conditions is entirely clinical; there

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are no diagnostic blood tests. The erythrocytesedimentation rate (ESR) is raised in the acute stage.Tests for rheumatoid factor and other autoantibodies are

negative; 60% of patients are HLA-B27 positive. X-raysare of no value in the acute stage of the disease, thoughsigns of sacroiliitis may appear with the development ofankylosing spondylitis.

Aspirated synovial fluid is inflammatory in nature with ahigh polymorphonuclear leucocyte count; the fluid issterile.

Treatment of autoimmune diseases

The conceptual basis for the treatment of autoimmunediseases is to reduce the patients immune responsesufficiently to eliminate the symptoms. Corticosteroids,such as prednione, are the mainstay of treatment, towhich antimetabolites (such as azathioprine andmethotrexate) can be added. The latter are nucleosideanalogues that inhibit DNA synthesis in the immune cells.Immunosuppressive therapy must be given cautiouslybecause of the risk of opportunistic infections.

Anti-inflammatory agents

Nonsteroidal anti-inflammatory drugs have been usedsince 1800s when salicin extracted from willow bark(1828), sodium salicylate (1875) and aspirin (1899) were

synthesized. A large numbers of these drugs, whicheither selectively or non-selectively inhibit the enzymecyclo-oxygenase (a synthetic enzyme for pros-taglandins)are currently in use to treat inflammatory disease.

Anti-malarial

Anti-malarial drugs have been used for the treatment ofSLEq and RA since early 1900s. The precise mechanismof action remains uncertain, but they have been shown toinhibit cytokine (IL-1 and IL-6) production in vitro. Theanti-malarial pass freely through cell membranes atneutral PH, but in acidic environments such asendosomes, they become protonated and can no longerdiffuse freely.

Anticytokine agents

The development of tumour necrosis factor- (TNF-)inhibitors in the 1990s ushered in a new era of therapy ofautoimmune disease using biological capable ofinterfering with the interactions between cytokines andtheir receptors.

Methotrexate

Methotrexate is a folic acid analog used extensively for


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Table 2. Research study.

Plant/title Activity

Ginseng In one study, it has been evaluated that ginseng polysaccharide decreases the expression of TNF-andinterferon-gamma (IFN-), and regulate the function of lymphocytes in enteric mucosal immune system incollagen-induced arthritis (CIA) rats. This study indicates that ginseng polysaccharide could be used in thetreatment of autoimmune disease (Hongyan et al., 2011)

O. basilicum It has been studied that aqueous extract of O. basilicumis a powerful natural immunomodulatory spiceinfluencing various types of immune-responses and have potential health effects (Tsai1 et al., 2011).

T. cordifolia It has been studied that T.cordifoliahas immunomodulatory properties, and is used for the treatment ofjaundice, skin diseases, diabetes and anemia (Chopra et al., 1982).

In one study, it has been evaluated that T. cordifoliaimproves the phagocytic and bactericidal activities inpatients suffering from polymorphism in surgical jaundice (Thatte et al., 1989). In one study, effect offeeding T. cordifoliahas been observed in broiler birds which were immunosuppressed withcyclophosphamide, and found a significant rise in antibody titer against ND virus with augmentation ofinflammatory reaction to skin contact sensitivity test (Kolte et al., 2007). Rege et al. (1989) and Bishavi et al.(2002) have proved the hepatoprotective effect of T. cordifolia.

W. somnifera Akram et al. (2010) studied the immunomodulant effect of W.somnifera.

Ocimum sanctum Modulates humoral immune response (Kujur, 2001; Krishnamohan et al., 1997; Kumar, 2003).

A. racemosus Stimulates both humoral and cell mediated immune responses (Kuttan et al., 1992).

the treatment of RA.

Anti-T-lymphocyte therapy

T-cells play a key role in the pathogenesis of type IVautoimmune reactions and also, they are critical forgenerating the T-cell dependent autoantibodies mediatingtype lll autoimmune diseases.

Anti-B-lymphocyte therapy

Rituximab is a cytotoxic chimeric human- mousemonoclonal antibody with a high affinity for CD20, a pan-B-cell surface antigen. It was developed originally for the

treatment of B-cell lymphomas.

Intravenous immunoglobulin

Intravenous immunoglobulin (IVIG) is a preparation ofhuman immunoglobulin pooled from thousands of healthyindividuals. It was originally developed for replacementtherapy in humoral immunnodeficiency syndromes buthas more recently become an important therapeuticmodality in severe autoimmune disorders, such asthrombocytppenic purpura, autoimmune haemolyticanaemia (AIHA), neuroimmunological diseases such asGuillain-Barre syndrome, SLE, certain forms of vasculitis,

and polymyositis dermatomyositis.

Autologous hematopoietic stem cell transplantation(HSCT)

Hematopoietic stem cells are the earliest progenitor cellsof the immune system and give rise to B and T-lymphocytes as well as antigen-presenting cells(monocytes, macrophages and dendritic cells). Therationale for HSCT as a therapy for autoimmune diseaseis based on the concept that the peripheral expansion ofauto-reactive T- and B-cell clones is central to thepathogenesis of autoimmunity.

DISCUSSION

An autoimmune disease occurs when the immunesystem fails to recognize the bodys own tissues as selfand mounts an attack on them. Disorders include RA,juvenile (insulin-dependent) diabetes, thyroiditis andmultiple sclerosis. Illnesses are divided into those thataffect much system. Autoimmune diseases are mostly ofunknown aetiology although genetic, hormonal,microbiological and environmental factors are known tobe implicated in their manifestation and severity.

Many herbal plant preparations are prescribed tostrengthen host resistance (Thatte and Dahanukar, 1986)due to their immunomodulatory activities (Table 2).Bodys immune system protects from disease andinfection (Damian et al., 2008). In an autoimmunedisease, immune system attacks healthy cells in your

body by mistake. Autoimmune diseases can affect many


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parts of the body. These diseases tend to run in families.There are more than 80 types of autoimmune diseases,and some have similar symptoms (Xiao et al., 1997).

Several studies have demonstrated the effects of herbalextracts on the immune system (Martino et al., 2010).Natural medicinal products have been traditionally usedfor the treatment of various complications in easterncountries, particularly China, India and Iran since theimmemorial time (Ram et al., 2009). In a healthy body,circulating antibodies attack and destroy pathogenicinvaders by means of humoral or cell-mediated immunity.In autoimmune disease, circ-lating antibodies seek attackand destroy self-antigens found in healthy tissue.Immunomodulator is a substance which stimulates orsuppresses the components of immune system includingboth innate and adaptive im-mune responses (Agarwal

and Singh, 1969). Tinospora cordifolia increasesleukocyte count (Manjrekar et al., 1999). Ocimumsanctumhas been reported to modulate humoral immuneresponse by releasing mediators for hypersensitivityreactions (Kujur, 2001; Krishnamohan et al., 1997;Kumar, 2003). Withania somnifera exhibitsimmunomodulatory activities and is usually used for thetreatment of gouty arthritis (Akram et al., 2010). A.racemosus stimulates both humoral and cell mediatedimmune responses in Swiss albino mice by Kuttan andKuttan (1992). A. racemosus extracts increasephagocytic activities of macrophages in vitro (Rege andDahanukar, 1993).

Conclusion

Autoimmune diseases may be greatly improved bystrengthening the immune system with nutritionalsupplements and by making healthy lifestyle changes indiet and stress reduction. The protocols needed mayinclude prescription drugs as well as the followingsupplements. Extracts of several plants have shownimpressive spectrum of biological activities as well asimmunomodulatory effects (Martino et al., 2010).

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