Cytokine profiles and inflammatory cells during HSV-1-induced acute retinal necrosis.
OBJECTIVE
To investigate infiltrating cells, cytokines, and kinetics of cytokine expression during acute retinal necrosis (ARN) in the uninoculated eye after inoculation of herpes simplex virus (HSV)-1 into the anterior chamber of one eye of BALB/c mice.


METHODS
At different time points after inoculation of 2 x 10(4) plaque-forming units (PFU) HSV-1 (KOS strain) or an equivalent volume of Vero cell extract in cell culture medium, the uninoculated eyes were enucleated. RT-PCRs for TNFalpha, IFNgamma, and IL-4 and immunohistochemical staining were performed to identify infiltrating cells and cytokines. Cytometric bead array was used to measure the levels of TNFalpha, IFNgamma, and IL-4 protein.


RESULTS
CD4(+) T cells, F4/80(+) macrophages, Gr-1(+) polymorphonuclear cells (PMNs), and CD19(+) B cells were detected in the uninoculated eye of virus-infected mice. Furthermore, RPE65(+) retinal pigment epithelial (RPE) cells and activated Muller cells were also detected in the ARN lesion. TNFalpha, IFNgamma, and IL-4 mRNA and protein were upregulated during the evolution of ARN in HSV-1-infected contralateral eyes compared with levels in control subjects. Immunohistochemistry revealed that cytokines were produced by infiltrating cells as well as by resident retinal cells.


CONCLUSIONS
The results of these studies support the idea that T cells and cytokines are actively involved in HSV-1 retinitis. They also suggest that PMNs, B cells, and/or macrophages, as well as resident retinal cells, such as RPE and activated Muller cells, also play a role in the pathogenesis of HSV-1 retinitis.
Zheng
Mei
M
Department of Cellular Biology and Anatomy, The Medical College of Georgia, Augusta, Georgia, USA.
Atherton
Sally S
SS
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D015828:Eye Infections, Viral / Q000378:metabolism / Q000821:virology*; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression; D006561:Herpes Simplex / Q000378:metabolism / Q000821:virology*; D018259:Herpesvirus 1, Human; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D007962:Leukocytes / Q000502:physiology*; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009457:Neuroglia / Q000502:physiology; D009504:Neutrophils / Q000502:physiology; D010857:Pigment Epithelium of Eye / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D015882:Retinal Necrosis Syndrome, Acute / Q000378:metabolism / Q000821:virology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D016207:Cytokines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma