Analysis of the immunological biomarker profile during acute Zika virus infection reveals the overexpression of CXCL10, a chemokine linked to neuronal damage

BACKGROUND Infection with Zika virus (ZIKV) manifests in a broad spectrum of disease ranging from mild illness to severe neurological complications and little is known about Zika immunopathogenesis. OBJECTIVES To define the immunologic biomarkers that correlate with acute ZIKV infection. METHODS We characterized the levels of circulating cytokines, chemokines, and growth factors in 54 infected patients of both genders at five different time points after symptom onset using microbeads multiplex immunoassay; comparison to 100 age-matched controls was performed for statistical analysis and data mining. FINDINGS ZIKV-infected patients present a striking systemic inflammatory response with high levels of pro-inflammatory mediators. Despite the strong inflammatory pattern, IL-1Ra and IL-4 are also induced during the acute infection. Interestingly, the inflammatory cytokines IL-1β, IL-13, IL-17, TNF-α, and IFN-γ; chemokines CXCL8, CCL2, CCL5; and the growth factor G-CSF, displayed a bimodal distribution accompanying viremia. While this is the first manuscript to document bimodal distributions of viremia in ZIKV infection, this has been documented in other viral infections, with a primary viremia peak during mild systemic disease and a secondary peak associated with distribution of the virus to organs and tissues. MAIN CONCLUSIONS Biomarker network analysis demonstrated distinct dynamics in concurrence with the bimodal viremia profiles at different time points during ZIKV infection. Such a robust cytokine and chemokine response has been associated with blood-brain barrier permeability and neuroinvasiveness in other flaviviral infections. High-dimensional data analysis further identified CXCL10, a chemokine involved in foetal neuron apoptosis and Guillain-Barré syndrome, as the most promising biomarker of acute ZIKV infection for potential clinical application.

Decrease in Dengue virus-2 infection and reduction of cytokine/chemokine production by Uncaria guianensis in human hepatocyte cell line Huh-7

ABSTRACT BACKGROUND Dengue fever may present hemorrhages and cavitary effusions as result of exacerbated immune responses. We investigated hydro-alcoholic extracts from leaves (UGL) and bark (UGB) of the medicinal species Uncaria guinanensis with respect to antiviral effects in Dengue virus (DENV) infection and in immunological parameters associated with in vivo physiopathological features. METHODS Chemical profiles from UGB or UGL were compared in thin layer chromatography and 1H nuclear magnetic resonance using flavonoid compounds and a pentacyclic oxindole alkaloid-enriched fraction as references. DENV-2-infected hepatocytes (Huh-7) were treated with extracts. Cell viability, DENV antigens and immunological factors were detected by enzyme-linked immunosorbent assay (ELISA) or flow cytometry. FINDINGS The UGL mainly differed from UGB by selectively containing the flavonoid kaempferitrin. UGB and UGL improved hepatocyte viability. Both extracts reduced intracellular viral antigen and inhibited the secretion of viral non-structural protein (NS1), which is indicative of viral replication. Reduction in secretion of macrophage migration inhibitory factor was achieved by UGB, of interleukin-6 by UGL, and of interleukin-8 by both UGB and UGL. MAIN CONCLUSIONS The U. guianensis extracts presented, antiviral and immunomodulatory effects for DENV and possibly a hepatocyte-protective activity. Further studies may be performed to consider these products as potential candidates for the development of an herbal product for the future treatment of dengue.

Polymorphisms in genes TLR1, 2 and 4 are associated with differential cytokine and chemokine serum production in patients with leprosy

BACKGROUND Leprosy or hansen’s disease is a spectral disease whose clinical forms mostly depends on host’s immune and genetic factors. Different Toll-like receptors (TLR) variants have been described associated with leprosy, but with some lack of replication across different populations. OBJECTIVES To evaluate the role of polymorphisms in genes TLR1, TLR2 and TLR4 and susceptibility to leprosy in a genetic case control study; to verify the association between genotypes of these markers and the immunological profile in the serum of patients with leprosy. METHODS Pre-designed TaqMan® assays were used to genotype markers at TLR1 (rs4833095, rs5743551), TLR2 (rs7656411, rs3804099) and TLR4 (rs1927914, rs1927911). A panel of cytokines and chemokines was accessed by enzime-linked immunosorbent assay (ELISA) test in the serum of a subgroup of patients with and without leprosy reactions. FINDINGS Our results show an association between the T allele of rs3804099 at the TLR2 gene and increased risk for leprosy per se [Odds ratio (OR) = 1.296, p = 0,022]. In addition, evaluating the association between different genotypes of the TLR1, 2 and 4 markers and cytokine/chemokine serological levels, IL-17 appears as an immunological marker regulated by the polymorphism of the three TLR genes evaluated, whereas different TLR1 genotypes were associated with differential production of IL-12p40 and MCP-1(CCL2). Furthermore, other relevant serum markers such as CXCL-10 and IL-6 seemed to be regulated by TLR2 variants and IL-1β was related to TLR4 genotypes. MAIN CONCLUSIONS All together our data points that the tested TLR markers may have a regulatory role in the immunity against Mycobacterium leprae, by driving the host’s production of key cytokines and chemokines involved in the pathogenesis of this disease.

Chemokines and immunity / Quimiocinas e imunidade

Chemokines are a large family of small cytokines and generally have low molecular weight ranging from 7 to 15kDa. Chemokines and their receptors are able to control the migration and residence of all immune cells. Some chemokines are considered pro-inflammatory, and their release can be induced during an immune response at a site of infection, while others are considered homeostatic and are involved in controlling of cells migration during tissue development or maintenance. The physiologic importance of this family of mediators is resulting from their specificity − members of the chemokine family induce recruitment of well-defined leukocyte subsets. There are two major chemokine sub-families based upon cysteine residues position: CXC and CC. As a general rule, members of the CXC chemokines are chemotactic for neutrophils, and CC chemokines are chemotactic for monocytes and sub-set of lymphocytes, although there are some exceptions. This review discusses the potential role of chemokines in inflammation focusing on the two best-characterized chemokines: monocyte chemoattractant protein-1, a CC chemokine, and interleukin-8, a member of the CXC chemokine sub-family.

Quimiocinas são uma grande família de pequenas citocinas e seu peso molecular varia de 7 a 15kDa. As quimiocinas e seus receptores são capazes de controlar a migração e a residência de células imunes. Algumas quimiocinas são consideradas pró-inflamatórias e podem ser induzidas durante a resposta imune no sítio de infecção, enquanto outras são consideradas homeostáticas e estão envolvidas no controle da migração celular durante o desenvolvimento ou a manutenção dos tecidos. A importância fisiológica dessa família de mediadores é resultado de sua especificidade − os membros da família de quimiocinas induzem ao recrutamento de subtipos bem definidos de leucócitos. Existem duas grandes subfamílias de quimiocinas baseadas na posição dos resíduos de cisteínas: CXC e CC. Como regra geral, membros da família de quimiocinas CXC são quimiotáticos de neutrófilos, e as quimiocinas CC são quimiotáticos de monócitos e subtipos de linfócitos, apesar de existirem algumas exceções. Esta revisão discute o potencial papel das quimiocinas na inflamação focando nas duas quimiocinas mais bem caracterizadas: a proteína quimioatraente de monócitos-1, uma quimiocina CC, e a interleucina 8, uma quimiocina membro da subfamília CXC.

Genetic correlates influencing immunopathogenesis of HIV infection.

Variability to HIV infection, its progression as well as responsiveness to antiretroviral therapy (ART) is observed among individuals including viraemia controllers or exposed uninfected, rapid versus slow progressors and ART responders compared to non responders. This differential responsiveness/ vulnerability to HIV-1 is governed by multiple host genetic factors that include HLA, cytokines, chemokines, their receptors and others. This review highlights the influence of these genetic factors on HIV/AIDS outcome; however, in India, the information in this area is very limited and most of these genetic studies have been conducted in Caucasian and South African populations. Considering, the population specific differences in the frequencies of protective or susceptibility favouring alleles and their influence on the disease outcome, it is of utmost importance to strengthen ongoing efforts towards defining largely unknown genetic propensity in Indian population, particularly by recruitment of large cohorts of well categorized exposed uninfected individuals, rapid, long term non progressors and elite viraemic controllers. Multi-parametric analysis of these potentially interactive immunogenetic variables in these cohorts may help to define potential targets for diagnostics and therapy in a population specific manner.

Role of IL-4 in an experimental model of encephalitis induced by intracranial inoculation of herpes simplex virus-1 (HSV-1) / Papel da IL-4 em modelo experimental de encefalite induzida pela inoculação intracraniana do herpes simplex vírus-1 (HSV-1)

Herpes simplex virus-1 (HSV-1) is a pathogen that may cause severe encephalitis in humans. In this study, we aimed to investigate the role of interleukin-4 (IL-4) in a model of HSV-1 brain infection. IL-4 knockout (IL-4-/-) and wild type (WT) C57BL/6 mice were inoculated with 10(4) plaque-forming units of HSV-1 by the intracranial route. Histopathologic analysis revealed a distinct profile of infiltrating cells at 3 days post-infection (dpi). Infected WT mice presented mononuclear inflammatory cells while IL-4-/- mice developed meningoencephalitis with predominance of neutrophils. IL-4-/- mice had diminished leukocyte adhesion at 3 dpi when compared to infected WT animals in intravital microscopy study. Conversely no differences were found in cerebral levels of CXCL1, CXCL9, CCL3, CCL5 and TNF-α between WT and IL-4-/- infected mice. IL-4 may play a role in the recruitment of cells into central nervous system in this acute model of severe encephalitis caused by HSV-1.

O vírus herpes simplex-1 (HSV-1) é um patógeno que pode causar encefalite grave em humanos. Neste estudo, buscamos investigar o papel da interleucina-4 (IL-4) no modelo de infecção intracerebral por HSV-1. Camundongos C57BL/6 selvagens (WT) e deficientes no gene IL-4 (IL-4-/-) foram inoculados com 10(4) unidades formadoras de placas de HSV-1 por via intracraniana. A análise histopatológica revelou um padrão distinto de infiltrado leucocitário. Camundongos WT infectados apresentaram infiltrado de células mononucleares, enquanto camundongos IL-4-/- desenvolveram meningoencefalite com predomínio de neutrófilos 3 dias pós-infecção (dpi). Animais IL-4-/- tiveram menor adesão de leucócitos 3 dpi quando comparados aos animais WT infectados à microscopia intravital. Em contrapartida, não foram encontradas diferenças nos níveis cerebrais de CXCL1, CXCL9, CCL3, CCL5 e TNF-α entre camundongos WT e IL-4-/- infectados. Esses resultados sugerem que IL-4 pode desempenhar um papel no recrutamento de células no sistema nervoso central neste modelo agudo de encefalite grave causada pelo HSV-1.

Sistema imunitário: Parte I. Fundamentos da imunidade inata com ênfase nos mecanismos moleculares e celulares da resposta inflamatória / Immune system: Part I. Fundamentals of innate immunity with emphasis on molecular and cellular mechanisms of inflammatory response

O sistema imunológico é constituído por uma intrincada rede de órgãos, células e moléculas, e tem por finalidade manter a homeostase do organismo, combatendo as agressões em geral. A imunidade inata atua em conjunto com a imunidade adaptativa e caracteriza-se pela rápida resposta à agressão, independentemente de estímulo prévio, sendo a primeira linha de defesa do organismo. Seus mecanismos compreendem barreiras físicas, químicas e biológicas, componentes celulares e moléculas solúveis. A primeira defesa do organismo frente a um dano tecidual envolve diversas etapas intimamente integradas e constituídas pelos diferentes componentes desse sistema. A presente revisão tem como objetivo resgatar os fundamentos dessa resposta, que apresenta elevada complexidade e é constituída por diversos componentes articulados que convergem para a elaboração da resposta imune adaptativa. Destacamos algumas etapas: reconhecimento molecular dos agentes agressores; ativação de vias bioquímicas intracelulares que resultam em modificações vasculares e teciduais; produção de uma miríade de mediadores com efeitos locais e sistêmicos no âmbito da ativação e proliferação celulares, síntese de novos produtos envolvidos na quimioatração e migração de células especializadas na destruição e remoção do agente agressor, e finalmente a recuperação tecidual com o restabelecimento funcional do tecido ou órgão.

The immune system consists of an intricate network of organs, cells, and molecules responsible for maintaining the body's homeostasis and responding to aggression in general. Innate immunity operates in conjunction with adaptive immunity and is characterized by rapid response to aggression, regardless of previous stimulus, being the organism first line of defense. Its mechanisms include physical, chemical and biological barriers, cellular components, as well as soluble molecules. The organism first line of defense against tissue damage involves several steps closely integrated and constituted by different components of this system. The aim of this review is to restore the foundations of this response, which has high complexity and consists of several components that converge to articulate the development of adaptive immune response. We selected some of the following steps to review: perception and molecular recognition of aggressive agents; activation of intracellular pathways, which result in vascular and tissue changes; production of a myriad of mediators with local and systemic effects on cell activation and proliferation, synthesis of new products involved in the chemoattraction and migration of cells specialized in destruction and removal of offending agent; and finally, tissue recovery with restoration of functional tissue or organ.

CD44 is involved in CXCL-12 induced acute myeloid leukemia HL-60 cell polarity

CXCL-12 and its receptor CXCR4 participate in breast cancer and melanoma cell metastasis to bone and lymphoid nodes. CD44, as a receptor for hyaluronic acid, is involved in lymphocyte recirculation, homing, adhesion and migration. But the role of CD44 in CXCL-12 induced leukemia cell migration still remains unclear. The present study showed that CXCL-12 stimulation induced the rapid internalization of CXCR4 and facilitated the formation of lamellipodia and uropod in acute leukemia cell line HL-60. CXCL-12 also induced CD44 translocation into the uropod, while CD44 remained evenly distributed on the untreated cell membranes. Results suggest that CD44 participates in CXCL-12 induced cell polarization and subsequent cell migration.

Seric chemokines and chemokine receptors in eosinophils during acute human schistosomiasis mansoni

The recruitment of circulating eosinophils by chemokines and chemokine receptors plays an important role in the inflammation process in acute human schistosomiasis. Our main focus has been on the plasma chemokines (CXCL8/CCL2/CCL3/CCL24) and chemokine receptors (CCR2/CCR3/CCR5/CXCR1/CXCR2/CXCR3/CXCR4) expressed by circulating eosinophils from acute Schistosoma mansoni infected patients (ACT). Our studies compared ACT patients and healthy individuals as a control group. Our major findings demonstrated a plethora of chemokine secretion with significantly increased secretion of all chemokines analysed in the ACT group. Although no differences were detected for beta-chemokine receptors (CCR2, CCR3 and CCR5) or alpha-chemokine receptors (CXCR3 and CXCR4), a significantly lower frequency of CXCR1+ and CXCR2+ eosinophils in the ACT group was observed. The association between chemokines and their chemokine receptors revealed that acutely infected schistosome patients displaying decreased plasma levels of CCL24 are the same patients who presented enhanced secretion of CCL3, as well as increased expression of both the CCR5 and CXCR3 chemokine receptors. These findings suggest that CCL24 may influence the kinetics of chemokines and their receptors and eosinophils recruitment during human acute schistosomiasis mansoni.

Effects of enteropathogenic bacteria & lactobacilli on chemokine secretion & Toll like receptor gene expression in two human colonic epithelial cell lines.

Background & objectives: The intestinal epithelium is part of the innate immune system responding to contact with pathogenic or commensal bacteria. The objective of this study was to compare innate responses of intestinal epithelial cell lines to pathogenic bacteria and to lactobacilli. Methods: Two human intestinal epithelial cell lines, HT29 (enterocyte-like) and T84 (crypt-like), were exposed to pathogenic bacteria representative of non invasive (Vibrio cholerae O1 and O139), adherent (enterohaemorrhagic Escherichia coli, EHEC) or invasive (Salmonella Typhimurium and Shigella flexneri) phenotypes and to non pathogenic Lactobacillus rhamnosus GG or Lactobacillus plantarum. Interleukin-8 (IL-8) was measured in culture supernatant by ELISA, while mRNA from cells was subjected to quantitative reverse transcriptase PCR for several other chemokines (CXCL1, CCL5 and CXCL5) and for Toll-like receptors (TLR) 2, 4, 5 and 9. Results: V. cholerae, S. Typhimurium, S. flexneri and EHEC induced IL-8 secretion from epithelial cells into the medium. Salmonella, Shigella and EHEC, but not V. cholerae, significantly increased mRNA expression of CXCL1. None of the pathogens induced CCL5 or CXCL5. Salmonella and Vibrio significantly increased TLR4 expression, while Vibrio and EHEC decreased TLR5 expression. EHEC also decreased TLR9 expression. Lactobacilli attenuated the IL-8 response of the cell lines to V. cholerae, Salmonella, and EHEC but did not significantly change the IL-8 response to Shigella. Interpretation & conclusions: Distinct patterns of epithelial cell chemokine responses were induced by the bacterial pathogens studied and these were modulated by commensal lactobacilli. Alterations in TLR expression by these pathogens are likely to be important in pathogenesis.

Immunological and non-immunological effects of cytokines and chemokines in the pathogenesis of chronic Chagas disease cardiomyopathy

The pathogenesis of Chagas disease cardiomyopathy (CCC) is not well understood. Since studies show that myocarditis is more frequent during the advanced stages of the disease, and the prognosis of CCC is worse than that of other dilated cardiomyopathies of non-inflammatory aetiology, which suggest that the inflammatory infiltrate plays a major role in myocardial damage. In the last decade, increasing evidence has shown that inflammatory cytokines and chemokines play a role in the generation of the inflammatory infiltrate and tissue damage. CCC patients have an increased peripheral production of the inflammatory Th1 cytokines IFN-³ and TNF-± when compared to patients with the asymptomatic/indeterminate form. Moreover, Th1-T cells are the main producers of IFN-³ and TNF-± and are frequently found in CCC myocardial inflammatory infiltrate. Over the past several years, our group has collected evidence that shows several cytokines and chemokines produced in the CCC myocardium may also have a non-immunological pathogenic effect via modulation of gene and protein expression in cardiomyocytes and other myocardial cell types. Furthermore, genetic polymorphisms of cytokine, chemokine and innate immune response genes have been associated with disease progression. We will review the molecular and immunological mechanisms of myocardial damage in human CCC in light of recent findings.

Cellular & molecular basis of HIV-associated neuropathogenesis.

Although a plethora of molecules have been implicated in the development of HIV associated dementia (HAD), the identity of the indispensable ones is still elusive. The action of various molecules appears to follow a cascade path with one molecule activating another thereby regulating the expression and modulation of the regulatory machineries. Two pathways have been proposed leading to HIV-induced central nervous system (CNS) injury. First involving neurotoxic effect of viral proteins and second, with immunomodulatory substances secreted by the infected cells playing vital role. The viral transfer from infected cells (for example, cells representing macrophage-microglial lineage) to uninfected cells (such as same cell type or nerve cells) occurring perhaps via virological synapse is also not well documented. While the mechanism underlying transfer of HIV-1 through blood-brain barrier is not clearly understood, macrophage-microglial cell lineages are undisputedly predominant cell types that HIV uses for transmission in CNS. The present review describes existing knowledge of the modus operandi of HIV-induced neuropathogenesis gathered through research evidences. of HIV-induced neuropathogenesis gathered through research Mechanisms by which regulatory molecules exploit such cell types in promoting neuropathogenesis would provide key insights in intersecting pathway(s) for designing intervention strategies.

The role of chemokines in Schistosoma mansoni infection: insights from human disease and murine models

Chemokines are a superfamily of low-molecular-weight cytokines that were initially described for their chemoattractant activity. It is now clear chemokines have several other activities that modulate immune processes. More than 50 chemokines ligands and at least 19 receptors have been described to date. Depending on the number of N-terminal cysteine residues, chemokines are grouped in the subfamilies CXC, CC, C or CX3C. A growing body of evidence suggests a role for chemokines in the pathogenesis of several inflammatory diseases. Our studies involving mice and humans infected with Schistosoma mansoni suggest an important role of the chemokine CCL3 and its receptors (CCR1 and CCR5) in the pathogenesis of severe schistosomiasis. We suggest that the differential activation of CCR1 or CCR5 during the course of schistosomiasis may dictate the outcome of the disease.

Human immunodeficiency virus and the central nervous system

The pandemic of HIV/AIDS continues to grow daily. Incident cases among women, intravenous drug users and ethnic minorities comprise the fastest growing segment of the HIV-infected population, and the number of HIV-infected individuals over the age of 50 is growing rapidly. Today, the central nervous system and the immune system are seen as main targets of HIV infection. Significant progress in the knowledge and treatment of AIDS has been obtained in recent years. The neurological manifestations directly related to HIV are acute viral meningitis, chronic meningitis, HIV-associated dementia (HAD), vacuolar myelopathy, and involvement of the peripheral nervous system.

Selective suppression of leukocyte recruitment in allergic inflammation

Allergic diseases result in a considerable socioeconomic burden. The incidence of allergic diseases, notably allergic asthma, has risen to high levels for reasons that are not entirely understood. With an increasing knowledge of underlying mechanisms, there is now more potential to target the inflammatory process rather than the overt symptoms. This focuses attention on the role of leukocytes especially Th2 lymphocytes that regulate allergic inflammation and effector cells where eosinophils have received much attention. Eosinophils are thought to be important based on the high numbers that are recruited to sites of allergic inflammation and the potential of these cells to effect both tissue injury and remodelling. It is hoped that future therapy will be directed towards specific leukocyte types, without overtly compromising essential host defence responses. One obvious target is leukocyte recruitment. This necessitates a detailed understanding of underlying mechanisms, particularly those involving soluble che-moattractants signals and cell-cell adhesion molecules.

Lessons in détente or know thy host: the immunomodulatory gene products of myxoma virus.

The poxvirus, myxoma virus, encodes within its genome at least eleven different proteins that compromise, skew, or disable the innate and adaptive responses of its hosts. In the laboratory rabbit, Oryctolagus cuniculus, these effects result in myxomatosis, a fatal condition characterized by skin lesions and systemic immunosuppression. Interestingly, while myxoma infection also causes skin lesions in its natural host and in natural populations of O. cuniculus in Australia where this novel host and the virus have co-evolved, the condition of myxomatosis does not ensue and infection is not fatal. In this review I discuss the biochemical properties of the characterized immunomodulatory proteins of myxoma virus, and their pathogenic effects in laboratory rabbits. Disruption of any one myxoma immunomodulatory gene diminishes the severity of the infection without compromising infectivity. Thus, the characterized immunomodulatory genes appear not to be required for a productive infection in vivo. The differences in the severity of their effects in laboratory-bred versus wild O. cuniculus suggest that the outcome of myxoma infection is a consequence of the interplay between the viral immunomodulatory gene products and the cells and molecules of the host immune system.

Eokines: synthesis, storage and release from human eosinophils

Eosinophils are prominent inflammatory cells in asthma and other allergic disorders, as well as in helminthic parasite infections. Recently, eosinophils have been reported to synthesize and store a range of regulatory proteins within their secretory granules (eokines). Eokines comprise a group of cytokines, chemokines, and growth factors which are elaborated by eosinophils. These proteins, and the messages which encode them, appear to be identical to those produced by lymphocytes and other tissues. Interestingly, immunoreactivity to many of these eokines has been found to co-localize to the eosinophil's secretory granules. In this review, we have discussed the repertoire of 18 eokines so far identified in eosinophils, and focused on four of these, namely, interleukin-2 (IL-2), IL-4, granulocyte/macrophage colony-stimulating factor (GM-CSF), and RANTES. These four eokines co-localize to the crystalloid granules in eosinophils, as shown in studies using subcellular fractionation and immunogold labeling in electron microscopy. During stimulation by physiological triggers, for example, with serum-coated particles, eosinophils release these mediators into the surrounding supernatant. In addition, eokines are likely to be synthesized within eosinophils rather than taken up by endocytosis, as show in detection of mRNA for each of these proteins using in situ hybridization, RT-PCR, and in the case of RANTES, in situ RT-PCR. Eokines synthesis and release from eosinophils challenges the commonly held notion that these cells act downstream of key elements in immune system, and indicate that they may instead belong to the afferent arm of immunity.

Las quimoquinas : una nueva familia de citoquinas reguladoras del proceso inflamatorio

La respuesta inmune e inflamatoria es regulada positiva y negativamente por medio de la secreción de mediadores solubles denominados citoquinas. Una nueva familia de citoquinas denominadas quimoquinas se compone por lo menos de 18 proteínas. Estas citoquinas presentan 20 a 45 por ciento de homología entre su secuencia de aminoácidos y poseen cuatro cisteínas conservadas que forman enlaces disulfuro en el extremo NH2 de la proteína. Con base en la secuencia de las primeras dos cisteínas, las quimoquinas se han dividido en dos subfamilias; las B-quimoquinas en las cuales las primeras dos cisteínas se encuentran separadas por un residuo no conservado (C-X-C) y las B-quimoquinas en las cuales estas dos cisteínas se encuentran adyacentes (C-C). Dentro de las actividades biológicas que comparten las alfa y las beta-quimoquinas se encuentran el incremento pasajero del calcio intracelular, cambios de la forma celular al interactuar con proteínas de la matriz celular, inducción de degranulación, incremento en la expresión de moléculas de adhesión celular (B2 integrinas), producción de prostaglandinas y leucotrienos e inducción de la explosión respiratoria en neutrófilos, basófilos, linfocitos T y monocitos principalmente. De manera particular, las B-quimoquinas ejercen una modulación de la respuesta inmunológica a través de varias actividades pleitrópicas, las cuales incluyen el reclutamiento de Células T y macrófagos en sitios de inflamación por medio de la regulación de su activación y proliferación. Se ha desmostrado recientemente que estas funciones pleiotrópicas de las quimoquinas juegan un papel importante en la regulación del proceso inflamatorio asociado al desarrollo de la patología de procesos autoinmunes y alérgicos.