IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME (IRIS)

Represent a manifestation of clinical phenomena that mainly occur in immunodeficient individuals upon reconstitution of immune responses [373]. In fact, in the last years IRIS has frequently been observed in HIV+ individuals responding to HAART, thus characterized by undetectable viremia and partial restoration of immunological functions, such as increased levels of memory (CD45RO) CD4+ T cells, due to redistribution from lymphoid tissue, followed by a steady rise of naive (CD45RA) lymphocytes as consequent of restoration of thymic activity [374].

However, due to the fact that HAART must be maintained for ever, secondary to the rapid HAART induced immunological reconstitution and restoration of pathogen-specific immunity [377] IRIS is common and due to a marked inflammatory reaction (necessary for the initial immunological responses). In the case of HIV+ individuals, where many opportunistic infections (OIs) can take place or latent infections be re-activated, IRIS can also be associated with active replication of mycobacterial and cryptococcal infections, fungi and herpes viruses [375,378,379]. Thus, due to the characteristic of HIV (i.e., integration into host DNA and presence of latent viral reservoirs, thus making HAART a life-long treatment) and the immunodeficient status of HIV+ individuals, IRIS is a consequence of immunodeficiency, in which only partial and inadequate immune reconstitution is obtained, and the life-long anti-retroviral treatment.

On the other side, IRIS can be fight by using anti-inflammatory molecules, as recently proposed (i.e., glucocorticoids and corticosteroids [377,378]) or by using HAART in combination with administration of cytokines.

In conclusion, the usage of cytokines in combination with HAART might represent a combination therapy aimed to a better control of HIV infection and of the immune system in immunodeficient individuals, thus providing an adequate clearance of OIs.

ACKNOWLEDGMENTS

This work has been partially supported by Europrise and NEAT Network of Excellence (EC-FP6).

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