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Abstract HPVs are DNA viruses that belong to the family papovaviridae. The DNA genome is divided into 3 main regions; the LCR, region of early proteins (E1-E8) and region of late proteins (L1, L2). HPV infection is confined to keratinocytes. HPV replication inside the cells occurs in a silent manner. There is no cytolysis or cell death and virus laden keratinocytes die of natural causes as desquamation or apoptosis. Viral proteins are only expressed at the upper layers of epidermis which are away of APCs. Clinical manifestations vary according to HPV type, the anatomical location and the immune status of the host. Warts have high prevalence during childhood. Sexual abuse is the main cause of 50% of all anogenital verruca in children, most frequently in girls and the incidence increases with the age of the child. Also, pregnant females have higher risk of developing HPV infection due to the existing immunological depression and the higher concentration of steroid hormones. Warts are treated with different modalities. Their combination usually has better results. Destructive methods are common but their main disadvantage is scarring. There are also virucidal and antimitotic methods. Every single wart must be treated with the previous mentioned methods. Different agents are used as an immunotherapy such as candida, MMR vaccine, PPD tuberculin, BCG vaccine and tricophyton. One or two target warts are injected; this clears not Summary 104 only the local warts but also distant warts unlike traditional wart therapies. Nowadays, prophylactic vaccines are used to prevent viral entry. They are type-specific. They are directed against L1and L2 and aim to produce high levels of L1 specific serum neutralizing antibodies and immune memory cells. The current available vaccines are bivalent HPV 16/18 and the Quadrivalent HPV 6/11/16/18 vaccines. They are directed against the high risk HPV types which turn to be carcinogenic. Also, there are therapeutic vaccines that eliminate infected cells expressing the viral onco-proteins E6 and E7. These vaccines are still under trial. Many researches used PPD tuberculin as an immunotherapy. Number of injections varied from 3, 4, 6 up to 12 injection times at 2-4 intervals. Side effects were reported as pain, edema and erythema at or around site of injection. None of them was severe for treatment to be discontinued. Most of them did an intradermal skin test before injection. Immunotherapies elicit delayed type hypersensitivity towards the injected antigen and also towards the viral antigens. This therapy has been found to be associated with the production of Th1 cytokines which activate Tc and NK cells to eradicate HPV infection. The local effect induced either by induction of a non specific inflammatory reaction or specific reaction by stimulating the action of Tc and T memory cells. The exact mechanism of action of immunotherapy is still unknown. It is believed that Th1 plays a major role in the immune response against HPV and both IL-12 and IFN-γ have Summary 105 antiviral activities. During the primary response to antigen, IL- 12 and IFN-γ are the cytokines which direct Th1 differentiation, and IL-4 directs differentiation of Th2 populations. Interleukin- 12 and IFN-γ coordinate the link between pathogen recognition by innate immune cells and the induction of specific immunity, by amplifying the Th1 response. Interleukin-12 is an IFN-γ inducer and also the antiviral activity of IL-12 is mediated through endogenous IFN-γ. Interleukin-12 acts in synergy with other activating cytokines such as IL-2, IL-18 and IL-27 for IFN-γ production. In this study, we measured IL-12 and IFN-γ levels before and after intralesional PPD tuberculin treatment in warts. Also, we compared their levels with levels in normal health individuals as a control. Patients had elevated pre-treatment levels of IL-12 and IFN-γ levels when compared to control individuals, which ensure their immunological role against HPV. There was no significant difference between pretreatment and post-treatment levels of IL-12 and IFN-γ. It is suggested that their maximum concentration was reached. Other factors play a role and affect resultant response to treatment. Interleukin-12 acts in synergy with IL-2 for IFN-γ induction from T-cells, NK cells. Similar synergy occurs with IL-18 on macrophages, dendritic cells, and B cells. Also, IL-12 synergizes with IL-27 on naïve T-cells. On the contrary, IL-10 acts as an immunosuppressive cytokine. It is a negative regulator for IL-12 and also inhibits IFN-γ production. As TGFSummary 106 β stimulates IL-10 production, so elevation of any of them will drive the immune system towards Th2 differentiation. These cytokines and these target cells are not the suspected to be deficient in this study, as IFN-γ is significantly elevated than in the control. IFN-γR deficiency may be the cause of HPV persistence. There are various forms of IFN-γR deficiency, partial or complete IFN-γR1 or IFN-γR2 deficiencies. Mutations in IFN- γR1 or IFN-γR2 genes result in defective IFN-γ mediated cell activation. This suggests that the outcome of viral infection in patients with IFN-γR deficiency depends partially on inherited factors, and that patients with IFN-γR deficiency may be resistant to certain viruses and susceptible to others. |