The Changes of Cytokines in Guillain Barré Syndrome: the Correlation With Clinical Manifestations and Skin Innervation
The Changes of Cytokines in Guillain Barré Syndrome: the Correlation With Clinical Manifestations and Skin Innervation
In order to increase our understanding about the pathogenic mechanism and the strategy of
 treatment in the subtypes of Guillain Barré syndrome, we will check the temporal changes of
 cytokines with different biological activities in serum and cerebrospinal fluid (CSF), check
 the titer of various anti-ganglioside antibodies, perform skin biopsy and correlate these
 data with the clinical findings such as severity and prognosis
In the past the nerve system has long been regarded as a privileged site of immune system due
 to (1) the absence of lymphatic drainage, which limits the immunological circulation; (2) the
 blood-brain barrier (BBB) or blood-nerve barrier (BNB), which limits the passage of immune
 cells and factors; (3) the low level of expression of MHC factors, particularly MHC II, in
 the resident cells of the nerve system and the lack of potent antigen presenting cells, such
 as dendritic or Langerhans' cells, both of which lead to reduced recognition of the neurons
 or nerves by the immune system; and (4) the presence of immunosuppressive factors such as
 TGF-b. which suppress the immune response in the nervous system.

 However in the past few years, the concept of privilege is revised, that is the differences
 in the immunological aspects between the nervous system and other organs are more
 quantitative than absolutely qualitative. Several lines of evidence indicate that BBB and BNB
 are not complete both anatomically and functionally and activated T cells can cross these
 barriers and traffic in and out the nervous system. The nervous system also contains a
 collection of immunologically resident cells, including professional or non-professional
 antigen presenting cells such as resident endoneurial or perivascular macrophage, glial
 cells, Schwann cells and endoneurial capillary endothelial cells, which are capable of
 synthesizing cytokines that were initially classified within the domain of the immune system
 and are found to express a range of appropriate specific receptors, both characteristics
 mediate the immunological processes in the nervous system.

 The nerve system is therefore a target of immune attacks. Many disorders of the central or
 peripheral nerve system are related to activation of the immune system. Immune mechanisms
 seem important in the pathogenesis and treatments of these disorders.

 Cytokines are a diverse group of soluble proteins and peptides which act as humoral
 regulators and modulate the activities of individual cells and tissues either under normal or
 pathological condition. Unlike the hormone, cytokines are usually made by more than one type
 of cells, have multiple target cells and multiple actions, and usually function in short
 acting radius. Constitutive cytokine production is usually low or absent and its production
 is promoted by certain stimuli at the transcription and translation level. The functions of
 cytokine are pleitropic and redundant. In embryogenesis and organ development, it acts as a
 regulator of miosis, differentiation, migration, cell growth and cell death; and in host
 defense response to infection, inflammation, autoimmune, trauma and metabolic injury, it not
 only stimulate immune cells to proliferate and differentiate but also regulate the
 progression and termination of immunological reaction. Some cytokines that make the
 inflammation progress are referred as pro-inflammatory cytokines. The major pro-inflammatory
 cytokines that are responsible for early responses are IL1, IL6, and TNF-alpha. Other
 pro-inflammatory mediators include IFN-gamma, TGF-beta, GM-CSF, IL11, IL12, IL17, IL18, IL8
 and a variety of other chemokines that chemoattract inflammatory cells. When these cytokines
 are produced or administered into human, they induce destruction of tissues, up-regulation of
 the synthesis of other pro-inflammatory cytokines by various immunological cells, and
 induction of systemic inflammatory reaction like fever and shock. Another immunoregulatory
 cytokines that counteract the inflammation or the production of pro-inflammatory cytokines
 are referred as anti-inflammatory cytokines. These mediators act mainly by the inhibiting the
 production of pro-inflammatory cytokines or by counteracting many biological effects of
 pro-inflammatory mediators and thus contribute to the control of the inflammatory responses.
 The major anti-inflammatory cytokines are IL4, IL10, and IL13. Other anti-inflammatory
 mediators are IL16, IFN-alpha, TGF-beta, G-CSF, as well as soluble receptors for TNF or IL6.
 It is supposed that the balance between pro-inflammatory cytokines and anti-inflammatory
 cytokines determines the net effect of an inflammatory response. In addition, cytokine
 responses are regulated by special subpopulations of CD4 (+) T-cells, called helper T cell.
 They provide help to other cells of the immune system in mounting immune responses by causing
 cell activation or the secretion of cytokines. Th1 cells stimulate strong cellular immunity
 but only weak and transient antibody responses. These cells produce a number of cytokines
 known asTh1 cytokines and including IL2, IFN-gamma, IL12 and TNF-beta. In contrast Th2 cells
 evoke strong antibody responses but relatively weak cellular activity. These cells produce
 cytokines that are known as Th2 cytokines and include IL4, IL5, IL6, IL10, and IL13. Th1 and
 Th2 cells can keep each other in check and prevent inflammatory reactions in response to
 pathogens getting out of control. However, imbalances may also precipitate inappropriate
 reactions. It is thought that some autoimmune disorders and allergies may be related to
 overactive Th1 or Th2 responses.

 Guillain-Barré syndrome (GBS) is clinically defined as an acute peripheral neuropathy over a
 time period of days or, at the most, up to 4 weeks. GBS may not be a single disease, but a
 variety of acute neuropathies with different clinical and electrophysiological
 manifestations. GBS is considered to be an autoimmune disease caused by cross reaction of
 infectious agents with auto-antigen. The triggering of autoimmunity depends both on the
 increase in immunogenicity of the target cell and the individual's own capability to
 recognize the antoantigens (HLA genes, T cell repertoire). The pathogenesis of GBS is not yet
 fully understood and GBS with variable clinical manifestations are supposed to be associated
 different immune mediated pathogenic mechanisms. By studying the GBS patients about their
 clinical manifestations, conventional laboratory studies, electrophysiological studies and
 skin biopsies and by evaluating the cytokine expression in the CSF and serum in different
 subtypes of GBS, we want to clarify the relationship between the immunological parameters and
 the clinical manifestations in GBS.
Inclusion Criteria:

 -  Progressive weakness of both legs and arms; areflexia; cranial nerve involvement (such
 as facial palsies); progression over days to 4 wks; recovery beginning 2-4 wks after
 progression ceases; elevated cerebrospinal fluid protein with <10 cells/µl;
 electrodiagnostic features of nerve conduction slowing or block.

 Exclusion criteria:

 -  nil